12,411 results on '"Biological Availability"'
Search Results
2. Safety, tolerability and pharmacokinetics of subcutaneous meropenem as an alternative to intravenous administration.
- Author
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Murray, Fionnuala, Yoo, Okhee, Brophy-Williams, Samuel, Rawlins, Matthew, Wallis, Steven C, Roberts, Jason A, Raby, Edward, Salman, Sam, and Manning, Laurens
- Subjects
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SUBCUTANEOUS infusions , *INTRAVENOUS therapy , *BODY mass index , *MEROPENEM , *GRAM-negative bacteria - Abstract
Background Subcutaneous delivery of antibiotics is a practical alternative to IV administration. Meropenem is commonly used to treat infections caused by resistant Gram-negative organisms. Methods This was a prospective, crossover self-controlled study in 11 stable inpatients established on meropenem. Participants received a single dose of subcutaneous meropenem, in 50 mL normal saline via gravity feed. Venous blood sampling was performed at baseline, 0.5, 1, 2, 4 and 8 h following the subcutaneous and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were assessed. Results Subcutaneous meropenem was well tolerated. The bioavailability of subcutaneous administration was 81.5% (95% CI 71.6%–93.2%). Increasing BMI was associated with slower absorption from subcutaneous tissue. Compared with IV, subcutaneous administration resulted in lower peak and higher trough concentrations. Despite the lower bioavailability observed, the PTA for free drug concentrations greater than the MIC for more than 40% of the time between doses was higher for subcutaneous than IV administration at MIC values between 0.03 and 8 mg/L. Simulated subcutaneous doses of 1.5 g twice daily, or 3 g continuous 24 h infusion had improved PTA relative to standard IV dosing of 1 g three times daily. Conclusions Subcutaneous meropenem appears to be well tolerated and has a favourable pharmacokinetic profile. Either 1.5 g twice daily or 3 g as a 24 h subcutaneous infusion could be considered for future evaluation. [ABSTRACT FROM AUTHOR]
- Published
- 2025
- Full Text
- View/download PDF
3. Clinically important interactions of macrolides and tetracyclines with dietary interventions—a systematic review with meta-analyses.
- Author
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Wiesner, Agnieszka, Zagrodzki, Paweł, Gawalska, Alicja, and Paśko, Paweł
- Subjects
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MACROLIDE antibiotics , *MINERAL supplements , *BIOAVAILABILITY , *ERYTHROMYCIN , *TETRACYCLINES , *AZITHROMYCIN - Abstract
Background Effective management of drug–food interactions is crucial for enhancing antibiotics' efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines. Methods We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines. We searched Medline (via PubMed), Embase and Cochrane Library databases up to December 2022. Risk of bias was assessed using Cochrane and NIH tools. Quantitative analyses were conducted if two or more comparable food-effect studies were available; otherwise, a qualitative summary was provided. Results We included 120 studies from 97 reports. Meta-analyses were conducted for 8 macrolides and 4 tetracyclines, with qualitative synthesis for 10 and 9, respectively. About 64% of the studies were open-label, crossover designs. Our assessment found that 37% of the studies had a high risk of bias, while only 6% had low risk. Food significantly affected 10 of 13 macrolides (77%) and 6 of 7 tetracyclines (86%). High positive effects on bioavailability were seen with extended-release azithromycin and clarithromycin, and erythromycin estolate. High negative impacts were observed with erythromycin propionate and stearate, azithromycin capsules, demeclocycline and omadacycline. Antacids and mineral supplements significantly decreased tetracyclines absorption. Milk and grapefruit juice showed variable impacts on absorption. Discussion Interactions depend on antibiotics' physicochemical characteristics, intervention type, drug formulation and potential patient factors. The quality of evidence was rated low due to outdated studies, methodological diversity and unequal data availability. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. 猪的蔗糖螯合微量元素高效利用 和节本增效技术方案研究.
- Author
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杨在宾 and 周建群
- Abstract
To study the technical scheme of high biological availability and increase efficiency by reducing costs of sucrose chelating trace elements in pigs A total of 600 000 commercial pigs were used to 4 initial tests, 2 final tests and 2 production application, to study biological utilization of sucrose chelating trace elements, by the measurement of the nutrients absorptivity, trace elements deposited and antioxidant indexes. The study were determined the biological utilization of sucrose chelatediron, copper, zinc and manganese was increased by 21%, 18%, 18% and 8%, respectively, compared to the corresponding sulfate. Through four net energy and nutrient utilization studies, provedsucrose chelating organic trace elements can reduce the pig digest ible energy 32-64 kcal/kg, crude protein 2.0%-3.0%, lysine 2.0%-3.0%, methionine 0.5%-1.0%, trypto phan 2.0%-4.0%, arginine 1.0%-2.0%, histidine 2.0%-5.0%, leucine 4.0%-5.0%, isoleucine 0.5%-1.0%, threonine 2.0%-3.0% and valine 3.0%-5.0%.The research determined the technical scheme of high biological availability and increase efficiency by reducing costs of sucrose chelating trace elements in pigs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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5. Population Pharmacokinetics of Dolutegravir in African Children: Results From the CHAPAS-4 Trial.
- Author
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Waalewijn, Hylke, Wasmann, Roeland E, Bamford, Alasdair, Gibb, Diana M, McIlleron, Helen M, Colbers, Angela, Burger, David M, Denti, Paolo, and team, the CHAPAS-4 trial
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AFRICANS , *SECONDARY analysis , *TENOFOVIR , *HIV infections , *DESCRIPTIVE statistics , *EMTRICITABINE , *PHARMACOKINETICS , *ANTI-HIV agents , *BIOAVAILABILITY , *CONFIDENCE intervals , *CHILDREN - Abstract
We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to <20 kg) or 50 mg (>20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.13%–30.8%) compared with zidovudine or abacavir with lamivudine. Nevertheless, concentrations remained above efficacy targets, confirming current dosing recommendations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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6. Can Dietary Iron Bioavailability Influence Colorectal Cancer Risk and Prognosis?
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Tara Rolić, Sanja Mandić, Iva Lukić, and Ines Banjari
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colorectal neoplasms ,dietary iron ,biological availability ,hepcidins ,projections and predictions ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Colorectal cancer (CRC) stands apart from other malignancies due to its pronounced association with dietary patterns. Approximately 70% of all CRC cases arise sporadically, and suboptimal dietary and lifestyle choices can override certain predisposing factors, including a family history of the disease. Hitherto, the most compelling evidence linking CRC risk has been attributed to heme iron, predominantly found in red and processed meats, although this form of iron constitutes a mere 20% of total dietary iron. The human organism maintains a remarkably intricate and tightly regulated iron homeostasis system owing to the deleterious consequences of both excessive and deficient serum iron levels. Dietary sources remain the sole means to replenish iron losses. Despite the abundant presence of iron in various food sources, its absorption, commonly referred to as bioavailability, is notably restricted due to an array of dietary inhibitors and homeostatic mechanisms.Consequently, a substantial 80% of ingested dietary iron is excreted in fecal matter, resulting in fecal iron concentrations that surpass those found in most body tissues by a tenfold margin. Prolonged exposure of the colorectum to excessive fecal iron, combined with concurrent physiological alterations, can instigate oncogenic processes leading to CRC. Notably, despite their recognized significance in CRC pathology, dietary habits, and lifestyle factors have been sporadically integrated into predictive models, primarily concerning CRC recurrence. Nonetheless, these models exhibit disparities in the dietary components, rendering them non-universally applicable. In light of these disparities, postulating that incorporating bioavailable iron, in conjunction with hepcidin levels, may offer superior predictive value for CRC risk assessment, and herein, elucidates the scientific foundation supporting this hypothesis.
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- 2024
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7. Mechanism of Action of Dihydroquercetin in the Prevention and Therapy of Experimental Liver Injury.
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Wei, Hewei, Zhao, Ting, Liu, Xinglong, Ding, Qiteng, Yang, Junran, Bi, Xiaoyu, Cheng, Zhiqiang, Ding, Chuanbo, and Liu, Wencong
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ALCOHOLIC liver diseases , *BIOAVAILABILITY , *FATTY liver , *TREATMENT effectiveness , *LIVER injuries , *LIVER cells - Abstract
Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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8. Can Dietary Iron Bioavailability Influence Colorectal Cancer Risk and Prognosis?
- Author
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Rolić, Tara, Mandić, Sanja, Lukić, Iva, and Banjari, Ines
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RISK assessment ,PACKAGED foods ,DIETARY patterns ,HOMEOSTASIS ,IRON regulatory proteins ,BEHAVIOR modification ,COLORECTAL cancer ,TOXIC substance exposure ,IRON compounds ,ENVIRONMENTAL exposure ,HEALTH behavior ,BIOAVAILABILITY ,BIOACCUMULATION ,DIET ,DISEASE risk factors ,DISEASE complications - Abstract
Colorectal cancer (CRC) stands apart from other malignancies due to its pronounced association with dietary patterns. Approximately 70% of all CRC cases arise sporadically, and suboptimal dietary and lifestyle choices can override certain predisposing factors, including a family history of the disease. Hitherto, the most compelling evidence linking CRC risk has been attributed to heme iron, predominantly found in red and processed meats, although this form of iron constitutes a mere 20% of total dietary iron. The human organism maintains a remarkably intricate and tightly regulated iron homeostasis system owing to the deleterious consequences of both excessive and deficient serum iron levels. Dietary sources remain the sole means to replenish iron losses. Despite the abundant presence of iron in various food sources, its absorption, commonly referred to as bioavailability, is notably restricted due to an array of dietary inhibitors and homeostatic mechanisms. Consequently, a substantial 80% of ingested dietary iron is excreted in fecal matter, resulting in fecal iron concentrations that surpass those found in most body tissues by a tenfold margin. Prolonged exposure of the colorectum to excessive fecal iron, combined with concurrent physiological alterations, can instigate oncogenic processes leading to CRC. Notably, despite their recognized significance in CRC pathology, dietary habits, and lifestyle factors have been sporadically integrated into predictive models, primarily concerning CRC recurrence. Nonetheless, these models exhibit disparities in the dietary components, rendering them non-universally applicable. In light of these disparities, postulating that incorporating bioavailable iron, in conjunction with hepcidin levels, may offer superior predictive value for CRC risk assessment, and herein, elucidates the scientific foundation supporting this hypothesis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. Genetic and clinical predictors of rifapentine and isoniazid pharmacokinetics in paediatrics with tuberculosis infection.
- Author
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Phaisal, Weeraya, Albitar, Orwa, Chariyavilaskul, Pajaree, Jantarabenjakul, Watsamon, Wacharachaisurapol, Noppadol, Ghadzi, Siti Maisharah Sheikh, Zainal, Hadzliana, and Harun, Sabariah Noor
- Subjects
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TUBERCULOSIS , *ORGANIC anion transporters , *ISONIAZID , *PHARMACOKINETICS , *P-glycoprotein , *PEDIATRICS - Abstract
Objectives Twelve weekly doses of rifapentine and isoniazid (3HP regimen) are recommended for TB preventive therapy in children with TB infection. However, they present with variability in the pharmacokinetic profiles. The current study aimed to develop a pharmacokinetic model of rifapentine and isoniazid in 12 children with TB infection using NONMEM. Methods Ninety plasma and 41 urine samples were collected at Week 4 of treatment. Drug concentrations were measured using a validated HPLC–UV method. MassARRAY® SNP genotyping was used to investigate genetic factors, including P-glycoprotein (ABCB1), solute carrier organic anion transporter B1 (SLCO1B1), arylacetamide deacetylase (AADAC) and N -acetyl transferase (NAT2). Clinically relevant covariates were also analysed. Results A two-compartment model for isoniazid and a one-compartment model for rifapentine with transit compartment absorption and first-order elimination were the best models for describing plasma and urine data. The estimated (relative standard error, RSE) of isoniazid non-renal clearance was 3.52 L·h−1 (23.1%), 2.91 L·h−1 (19.6%), and 2.58 L·h−1 (20.0%) in NAT2 rapid, intermediate and slow acetylators. A significant proportion of the unchanged isoniazid was cleared renally (2.7 L·h−1; 8.0%), while the unchanged rifapentine was cleared primarily through non-renal routes (0.681 L·h−1; 3.6%). Participants with the ABCB1 mutant allele had lower bioavailability of rifapentine, while food prolonged the mean transit time of isoniazid. Conclusions ABCB1 mutant allele carriers may require higher rifapentine doses; however, this must be confirmed in larger trials. Food did not affect overall exposure to isoniazid and only delayed absorption time. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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10. Bioavailability comparison study of two benzathine benzylpenicillin 1,200,000 IU intramuscular formulations in healthy male participants under fast state
- Author
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Vinicius Marcondes Rezende, Paulo Galvinas, Carlos Sverdloff, Camila Leles Guimaraes, Anne Silveira, Camila Aihara, Marcia Aparecida Antonio, and Renata Di Sessa
- Subjects
Benzathine benzylpenicillin ,Penicillin G ,Bioavailability ,Biological availability ,Pharmacokinetics ,Medicine - Abstract
Introduction: Benzathine benzylpenicillin G is a drug present in the list of essential medicines of the World Health Organization and largely used in Brazil, where this antibiotic is used for treating pneumonias, pharyngitis, syphilis, and other infections caused by Gram-positive bacteria, being one of the most prescribed antibiotics of the public healthcare system. Objective: The objective of this study was to evaluate the relative bioavailability of two formulations of benzathine benzylpenicillin (Benzetacil®) 1,200,000 IU, both manufactured by Eurofarma Laboratórios S/A, by comparison of plasma levels of both drugs administered intramuscularly, evaluating the pharmacokinetic parameters: Cmax and AUC0-t, being t=672 h. Methods: A randomized, parallel, open-label study with one treatment and one period in 168 healthy male volunteers. Subjects received the test or reference formulations by intramuscular injection. A total of 20 blood samples were collected after administration for plasmatic quantification of the drug by LC-MS/MS along 672 h. Results: Both formulations were considered well tolerated, and no serious adverse event was reported during the trial. Cmax and AUC0-t were compared: the rate between test and reference formulations for Cmax was 97.75% with confidence interval (CI) (86.34–110.67%) and power 90.55%. The rate between test and reference formulations for AUC0-t was 91.15% CI (85.29–97.42%) and power of 99.99%. The rate between test and reference formulations for AUC0-inf was 87.98% with CI (81.29–95.23%) and power of 99.85%. Conclusion: Reference and test formulations were shown to be statistically bioequivalents according to their rate and extension of absorption, based on ANVISA criteria.
- Published
- 2024
- Full Text
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11. Do dietary interventions exert clinically important effects on the bioavailability of β-lactam antibiotics? A systematic review with meta-analyses.
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Wiesner, Agnieszka, Zagrodzki, Paweł, and Paśko, Paweł
- Subjects
- *
DRUG accessibility , *DRUG-food interactions , *ANTIBIOTICS , *MINERAL supplements , *PENICILLIN G , *LACTAMS , *BETA lactam antibiotics , *OXACILLIN - Abstract
Background Managing drug–food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics. Methods We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. Results Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or C max decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or C max increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). Conclusions Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. Efects of biochar combined with nitrogen fertilizer on ryegrass remediation of cadmium‑contaminated soil.
- Author
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Li, F., Liu, H., Zhong, H., Dong, L., Tang, Y., and Ge, Y.
- Abstract
In order to reduce the harm of cadmium (Cd) in soil, the effects of biochar combined with nitrogen fertilizer (NO
3 − –N) on Cd enrichment in ryegrass were studied. In this study, soil contaminated with 0.3 mg/kg, 3 mg/kg and 5 mg/kg Cd was subjected to 6 treatments (CK: Neither NO3 − –N nor shell biochar; BC: 5% shell biochar; BNX: shell biochar + X mg/mL NaNO3 solution, X = 1, 2, 5, 10), the remediation effect of biochar combined with NO3 − –N on Cd-contaminated soil was investigated. A single application of biochar can effectively fix free Cd in the soil. Under different concentrations of Cd pollution, the maximum removal rates of Cd under different NO3 − –N levels could reach 30.23%, 36.06%, and 30.90%, respectively. In addition, it was found that the organic matter of medium and low Cd-polluted soil was positively correlated with the available Cd content. In contrast, in the case of higher Cd pollution, organic matter has less influence on the effective Cd content. Combined with correlation analysis, pH plays a key role in Cd morphological change and Cd enrichment. When the mass ratio of NO3 − –N and biochar is about 5:1 ~ 10:1, Cd in soil can be reduced more effectively and quickly, the phytoremediation period can be shortened, and the biological removal rate and Cd enrichment can be increased. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
13. Population pharmacokinetics of posaconazole in allogeneic haematopoietic stem cell transplant patients.
- Author
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Selby, Philip R, Heffernan, Aaron J, Yeung, David, Warner, Morgyn S, Peake, Sandra L, Hahn, Uwe, Westley, Ian, Shakib, Sepehr, and Roberts, Jason A
- Subjects
- *
HEMATOPOIETIC stem cells , *STEM cell transplantation , *DRUG monitoring , *ORAL drug administration , *PHARMACOKINETICS - Abstract
Background Invasive fungal disease (IFD) in the early post-allogeneic HSCT (alloHCT) period is associated with increased likelihood of catastrophic outcomes. The utility of oral modified release (MR) posaconazole tablets is limited by reduced drug absorption from gastrointestinal toxicity induced by cytotoxic chemotherapy, necessitating a switch to the IV posaconazole formulation. Objectives To describe the population pharmacokinetics of posaconazole for oral MR and IV formulations in alloHCT patients and determine dosing regimens likely to achieve therapeutic exposures. Methods We performed a prospective observational pharmacokinetic study in adult patients in the early post-alloHCT period requiring a change in posaconazole formulation (oral to IV). Samples were analysed using a validated LC-MS/MS method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. Results Twenty patients aged between 21 and 70 years were included in the study. A two-compartment model, incorporating mucositis/diarrhoea to modify the bioavailability for oral administration best described the data. To achieve ≥90% PTA, simulations showed that higher than currently recommended doses of oral MR posaconazole were required for prophylaxis C min targets (≥0.5 and ≥0.7 mg/L), while increased doses of both formulations were required for IFD treatment PK/PD targets, with patients experiencing oral mucositis/diarrhoea unlikely to achieve these. Conclusions Increased doses of posaconazole should be considered for both prophylaxis and treatment of IFD to increase the proportion of alloHCT patients achieving therapeutic exposures, particularly the oral formulation in patients with mucositis and/or diarrhoea. Posaconazole therapeutic drug monitoring should be considered for all formulations in this setting. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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14. Preparation and characterization of morphine gelatine microspheres
- Author
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Xin Jin, Jun Ji, and Yonghai Sun
- Subjects
morphine ,microspheres ,biological availability ,analgesia ,pharmacokinetics ,Polymers and polymer manufacture ,TP1080-1185 - Abstract
Morphine is a widely used opioid analgesic. However, standard morphine dosages and administration methods exhibit a short half-life and pose a risk of respiratory depression. Sustained-release microspheres can deliver prolonged efficacy and reduce side effects. We present a new controlled-release morphine gelatine microsphere (MGM) prepared using an emulsification-crosslinking strategy. The gelatine microsphere design improves the bioavailability of morphine. And it not only increases the clinical analgesic efficacy but also the safety of clinical medication through a gradual, sustained release. Besides, we describe MGMs’ preparation, release, pharmacodynamics, and pharmacokinetics. And the drug metabolism pathway. We calculate the release rate of morphine by measuring plasma morphine concentration over time and pharmacokinetic parameters. It optimized the manufacturing process of MGMs, which makes the analgesic effect have a longer duration. MGMs analgesic effect shows dose dependence. After they were administrated, MGMs were released more slowly. Peak concentration was reduced, and the relative bioavailability improved. It even reached 88.84%. Its pharmacokinetic process was consistent with the two-component first-order absorption model. MGMs deliver sustained-release and long-action pharmacokinetics. It shows design goals of improving drug bioavailability, prolonging drug residence time in vivo, and maintaining stable blood drug concentration.
- Published
- 2023
- Full Text
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15. Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52 weeks: a phase III double-blind, randomized placebo-controlled trial.
- Author
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Bhat, Sreeja S., Ahmed, Sakir, Reji, Reshma, Mehta, Pankti, Paul, Aby, Mohanan, Manju, Babu, Sageer, Vinayak, Biju, Vijayan, Anuroopa, Nalianda, Kaveri K., Joseph, Sanjana, Narayanan, K., Padmaja, R., Alex, Glaxon, and Shenoy, Padmanabha
- Subjects
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ANTIRHEUMATIC agents , *RHEUMATOID arthritis , *CURCUMIN , *OVERALL survival - Abstract
Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97–1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels. Trial registration: CTRI/2018/04/013279. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
16. Preparation and characterization of morphine gelatine microspheres.
- Author
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Jin, Xin, Ji, Jun, and Sun, Yonghai
- Subjects
GELATIN ,MORPHINE ,DRUG metabolism ,OPIOID analgesics ,DRUG bioavailability ,MICROSPHERES ,BIOAVAILABILITY - Abstract
Morphine is a widely used opioid analgesic. However, standard morphine dosages and administration methods exhibit a short half-life and pose a risk of respiratory depression. Sustained-release microspheres can deliver prolonged efficacy and reduce side effects. We present a new controlled-release morphine gelatine microsphere (MGM) prepared using an emulsification-crosslinking strategy. The gelatine microsphere design improves the bioavailability of morphine. And it not only increases the clinical analgesic efficacy but also the safety of clinical medication through a gradual, sustained release. Besides, we describe MGMs' preparation, release, pharmacodynamics, and pharmacokinetics. And the drug metabolism pathway. We calculate the release rate of morphine by measuring plasma morphine concentration over time and pharmacokinetic parameters. It optimized the manufacturing process of MGMs, which makes the analgesic effect have a longer duration. MGMs analgesic effect shows dose dependence. After they were administrated, MGMs were released more slowly. Peak concentration was reduced, and the relative bioavailability improved. It even reached 88.84%. Its pharmacokinetic process was consistent with the two-component first-order absorption model. MGMs deliver sustained-release and long-action pharmacokinetics. It shows design goals of improving drug bioavailability, prolonging drug residence time in vivo, and maintaining stable blood drug concentration. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
17. Co-administration of herbal inhibitors of P-glycoprotein with renal drugs enhance their bioavailability– In silico approach
- Author
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Chandana Roy and Pratiti Ghosh
- Subjects
multidrug resistance ,efflux transporter ,biological availability ,herbs ,docking ,Medicine (General) ,R5-920 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Introduction: Multidrug resistance (MDR) is primarily associated with reduced intracellular drug accumulation owing to overexpression of p-glycoprotein, an active efflux transporter. Competitive inhibition or allosteric modulation of p-glycoprotein may alter the pharmacokinetics of the drugs that serve as substrates, resulting in enhanced drug bioavailability and tissue penetration. This study endeavors to assess the efficacy of the components of reno-protective herbs in the inhibition of p-glycoprotein activity thereby enhancing the possibility of the retention of co-administered renal medications inside the target cells. Methods: Drug-likeness and pharmacokinetic properties were determined to ensure the safety and efficacy of herbal constituents. Molecular docking employing the CDOCKER module of Discovery Studio was performed to investigate the binding affinity between the active constituents and the p-glycoprotein receptor (6C0V). Molecular dynamics simulation was utilized to further assess the stability of the complex of receptors with the component bearing its maximal affinity. Results: The analyses suggested that the inhibitors viz., atisine, kutkin, and embelin from Aconitum heterophyllum, phylloquinone from Calendula officinalis, stigmasterol from Paederia foetida, and convallamarogenin from Convallaria majalis demonstrated maximum binding affinity towards p-glycoprotein. Conclusion: Atisine may thus be identified as the lead compound in the augmentation of drug bioavailability inside the cell, along with its reno-protective efficacy.
- Published
- 2023
- Full Text
- View/download PDF
18. Safety and pharmacokinetic comparison between fenofibric acid 135 mg capsule and 110 mg entericcoated tablet in healthy volunteers.
- Author
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Yu-Bin Seo, Jae Hoon Kim, Ji Hye Song, WonTae Jung, Kyu-Yeol Nam, Nyung Kim, Youn-Woong Choi, SangMin Cho, Do-Hyung Ki, Hye Jung Lee, JungHa Moon, SeungSeob Lee, JaeHee Kim, Jang Hee Hong, Jung Sunwoo, and Jin-Gyu Jung
- Subjects
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ENTERIC-coated tablets , *PHARMACOKINETICS , *KOREANS , *VOLUNTEERS , *DOSAGE forms of drugs , *FASTING , *DEGLUTITION , *ACID-base imbalances - Abstract
This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a noncompartmental method with Phoenix WinNonlin®. A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (Cmax) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795-0.9614) and 0.8630 (0.8472-0.8791) in the fasting study and 1.0926 (1.0102-1.1818) and 0.9998 (0.9675-1.0332) in the fed study, respectively. The time to reach Cmax of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
19. Nutrient Interaction and Health Risk Assessment of Cereal Grains on Nigerian’s Markets
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N.A. Obasi, S.E. Obasi, L.O. Ajala, G.O. Aloh, C. Aloke, S.S. Ogundapo, and G.N. Onyeji
- Subjects
edible grains ,minerals ,nutrients ,biological availability ,risk assessment ,nigeria ,Food processing and manufacture ,TP368-456 - Abstract
Background: Cereals are the most staple foods in human diet and the main components of the daily diet. This work was designed to determine the level of essential and non-essential elements, the in vitro bioavailability, interrelationship, and associated health risk in consumed cereal grains in Nigeria to assess their safety and wholesomeness. Methods: The contents of phytate, oxalate, and some major-, trace- and potentially toxic elements were determined in 36 samples of barley, maize, millet, rice, sorghum, and wheat marketed in Nigeria. Results: The data showed variable significant (p
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- 2022
20. An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants.
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Marwaha, Raman Kumar, Verma, Manish, Walekar, Ajit, Sonawane, Rakesh, and Trivedi, Chirag
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ANALYSIS of variance ,BIOAVAILABILITY ,EMULSIONS ,CHOLECALCIFEROL ,RANDOMIZED controlled trials ,DESCRIPTIVE statistics ,STATISTICAL sampling ,CROSSOVER trials ,NANOPARTICLES - Abstract
Nanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants. In this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18–45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC 0–120h ], maximum observed drug concentration [C max ], time to reach maximum drug concentration [T max ], terminal half-life [T ½el ], and terminal elimination rate constant [K el ]) were estimated using baseline corrected data and analyzed using analysis of variance. Among the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC 0–120h. Similarly, C max of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC 0–120h and C max were 23.22% and 26.51%, respectively. The T max , T ½el , and K el were comparable for both the formulations. No adverse effects were noted with either of the two formulations. Nanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants. [ABSTRACT FROM AUTHOR]
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- 2023
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21. Nutrient Interaction and Health Risk Assessment of Cereal Grains on Nigerian’s Markets.
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Obasi, N. A., Obasi, S. E., Ajala, L. O., Aloh, G. O., Aloke, C., Ogundapo, S. S., and Onyeji, G. N.
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HEALTH risk assessment ,FOOD safety ,SORGHUM ,MILLETS ,OXALATES - Abstract
Background: Cereals are the most staple foods in human diet and the main components of the daily diet. This work was designed to determine the level of essential and non - essential elements, the in vitro bioavailability, interrelationship, and associated health risk in consumed cereal grains in Nigeria to assess their safety and wholesomeness. Methods: The contents of phytate, oxalate, and some major -, trace - and potentially toxic elements were determined in 36 samples of barley, maize, millet, rice, sorghum, and wheat marketed in Nigeria. Results: The data showed variable significant (p<0.05) levels of elements, phytate, and oxalate in the cereals but they were below European commission maximum permissible limits. Estimated daily intakes (EDIs) of elements in the cereals were all below maximum permissible limits set by European Food Safety Authority (EFSA). Hazard Quotient (HQ) and Hazard Index (HI) values, though higher in children than adults, were less than one except in wheat and sorghum. The incremental lifetime Cancer Risk (CR) and Total Cancer Risk (TCR) values were below the threshold limit. Conclusion: This study revealed that barley, maize, millet, rice, sorghum, and wheat available in Nigeria markets contain varying quantities of essential elements, potentially toxic elements, and antinutrients. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Intestinal microbiota-mediated dietary fiber bioavailability
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Kangxiao Guo, Zihan Yao, and Tao Yang
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dietary fiber ,intestinal microbiota ,short-chain fatty acids ,biological availability ,mediated ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Dietary fiber is a kind of carbohydrate that cannot be digested and absorbed by the small intestine of humans but can be fermented in all or part of the large intestine and is significantly healthy for the human body. With the improvement in living standards, people pay more attention to their intestinal health, and the relationship between dietary fiber, intestinal microecological and body physiological balances, and their molecular connection mechanism has become a research hot spot. In this study, we reviewed its mediated bioavailability to provide a basis for the rational classification of dietary fiber and to guide the development of new healthy foods and the deep processing of food and its application.
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- 2022
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23. Albedo flour of Tahiti lime (Citrus latifolia Tanaka) as a strategy to control bone fragility in ovariectomized rats
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Pedro Henrique Costa Calmon Rodrigues, Savio Ernesto da Fonseca, Angela de Almeida Pretti Rocha, Paloma de Paula Pereira, Roberta Valeriano dos Santos, Girlandia Alexandre Brasil, Marcela Nascimento Sertorio, and Christiane Mileib Vasconcelos
- Subjects
Citrus ,Calcium ,Biological availability ,Bone disease ,Ovariectomy ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Summary: Introduction: Experimental studies have shown that the albedo of Tahiti lime (Citrus latifolia Tanaka) is rich in calcium, but little is known about its bioavailability. Objective: Produce flour from the albedo of Tahiti lime, characterizing it and assessing the bioavailability of calcium. Methods: Centesimal composition, mineral calcium content, phenolic compounds, antioxidant activity and physical analysis were performed. Female rats were divided in groups: OVX (ovariectomized) and SHAM (sham-operated). After surgery, the animals were redivided and treated for 60 days: SHAMc: control diet (CD); SHAMa: CD+130 mg of albedo flour/kg body weight (BW); OVXc: CD; OVXa: CD+130 mg of albedo flour/kg BW. Serum biochemical and radiological analysis were performed. Results: Albedo flour of Tahiti lime showed a product with low moisture (9.39%), abundant calcium content (0.66%) and moderate antioxidant power (0.89 μg/ml). The results in vivo point towards a positive interference of the albedo in the studied groups. Hepatosomatic index showed that OVXa (3.16±0.56) did not differ from the SHAMc (3.86±0.84) and SHAMa (3.85±0.52), which may indicate that the administration of albedo contributed to the development of the group. The cortical region of femoral medial diaphysis and the medullar region of tibial medial diaphysis were higher (p≤0.05) in the OVXa group when compared to OVXc, the latter being also higher than SHAM groups, suggesting efficacy in preventing dysfunctions related to bone changes. Conclusion: The albedo of Tahiti lime showed relevant characteristics and the results from the in vivo experiment are suggestive of effectiveness in preventing dysfunctions related to bone changes.
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- 2021
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24. Relative Bioavailability of Trace Minerals in Production Animal Nutrition: A Review.
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Byrne, Laurann and Murphy, Richard A.
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- *
BIOAVAILABILITY , *TRACE elements , *SWINE nutrition , *POULTRY feeding , *IRON , *DIETARY supplements , *ANIMAL nutrition , *NUTRITION - Abstract
Simple Summary: This is a comprehensive review containing the most up-to-date information on the relative bioavailability of selected trace minerals (copper, iron, manganese and zinc) used in ruminant, poultry and swine nutrition. Inorganic and organic forms of the trace minerals are included, and the differences between the product types are highlighted. Building on previously published tables and data, this review incorporates studies on newly developed products and concepts not previously discussed. Extensive data tables are included, providing a valuable reference guide. Methods to calculated relative bioavailability of the minerals are discussed and reasons for potential variance are noted. Detailed background information on uptake mechanisms to aid understanding of mineral transport is also contained in the current review. The importance of dietary supplementation of animal feeds with trace minerals is irrefutable, with various forms of both organic and inorganic products commercially available. With advances in research techniques, and data obtained from both in-vitro and in-vivo studies in recent years, differences between inorganic and organic trace minerals have become more apparent. Furthermore, differences between specific organic mineral types can now be identified. Adhering to PRISMA guidelines for systematic reviews, we carried out an extensive literature search on previously published studies detailing performance responses to trace minerals, in addition to their corresponding relative bioavailability values. This review covers four of the main trace minerals included in feed: copper, iron, manganese and zinc, and encompasses the different types of organic and inorganic products commercially available. Their impact from environmental, economic, and nutritional perspectives are discussed, along with the biological availability of various mineral forms in production animals. Species-specific sections cover ruminants, poultry, and swine. Extensive relative bioavailability tables cover values for all trace mineral products commercially available, including those not previously reviewed in earlier studies, thereby providing a comprehensive industry reference guide. Additionally, we examine reasons for variance in reported relative bioavailability values, with an emphasis on accounting for data misinterpretation. [ABSTRACT FROM AUTHOR]
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- 2022
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25. Permeation enhancement effects of leaf materials from different aloe species on in vitro and ex vivo nasal epithelial models
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Werner Gerber, Dewald Steyn, Awie Kotzé, Hanna Svitina, Ché Weldon, and Josias Hamman
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aloe ,biological availability ,herb-drug interactions ,intranasal administration ,medicinal plants ,tight junctions ,Medicine (General) ,R5-920 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Introduction: The nasal route of drug administration offers an alternative way for oral drug delivery and has the benefit of avoiding first-pass metabolism through drug delivery directly into the systemic circulation. The drug absorption enhancing effects of selected aloe leaf materials have been shown across various delivery routes, but their efficacies in this regard across nasal epithelia have not yet been investigated. The aim of this study was to determine the effects of gel and whole leaf extract materials from three selected aloe species (Aloe vera, Aloe ferox and Aloe muth-muth) on FITC-dextran 4400 permeation across two nasal epithelial models. Methods: Permeation of FITC-dextran 4400 and histological studies were conducted on both RPMI 2650 cell layers and excised sheep nasal mucosa, while toxicity studies were conducted using a neutral red assay on the RPMI 2650 cell model. Results: Significantly increased (P ≤ 0.05) apparent permeability coefficient (Papp) values of FITC-dextran 4400 in the presence of the aloe materials as compared to the control were found with all three aloe species at the highest concentrations (1.5% and 3% w/v) in the RPMI 2650 cell line, while only Aloe muth-muth at the highest concentration exhibited significantly (P ≤ 0.05) higher Papp values across the excised tissue model. Histological and neutral red analysis showed that Aloe vera materials exhibited detrimental effects, Aloe muth-muth only showed slight effects on cell viability and Aloe ferox exhibited no effect on the nasal epithelium. Conclusion: This in vitro study showed for the first time the potential of Aloe ferox and Aloe muth-muth leaf materials to enhance nasal drug delivery without causing damaging effects on the epithelium, while Aloe vera enhanced nasal drug delivery with detrimental effects as determined by means of cytotoxicity assays and histological analysis.
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- 2020
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26. Nanoclays in food products: benefits and possible risks (literature review)
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I.V. Gmoshinski, O.V. Bagryantseva, O.V. Arnautov, and S.A. Khotimchenko
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nanoclays ,aluminum ,food additive ,exposure ,biological availability ,toxicity ,intestinal microbiocenose ,Medicine - Abstract
Nanoclays (NC) are aluminosilicates that consist of layers (nano-plates) being 1–2 nanometers thick and having a diameter over 1 µm, nanotubes, and nano-disks. Due to such structure and their ion-exchange and sorption properties as well as gas permeability NC are widely used in industries, agriculture, and medicine. Gas-barrier composite packages are made from hydrophobic NC modified with cation-active surface-active substances. A person can be orally exposed to NC due to their migration from packages into food products and drinks, when NC are applied in medicine as enteric sorbents and anti-bacterial preparations, they can be introduced with food additives and residual quantities of technological auxiliaries as well as in case when food products and agricultural raw materials are accidentally contaminated with clays. Multiple research works dwell on experiments with NC performed with model systems in vitro when NC turned out to be cytotoxic for various cell types, and it was more apparent for hydrophobic NC than for their non-modified analogues. Minimum effective NC dose varied from 0.001 to 1 mg/ml in various in vitro tests. In vitro research on NC toxicity yielded somewhat contradictory results. Though NC didn’t seem to have apparent acute toxicity (IV hazard category, LD50 > 5,000 mg/kg), results obtained via sub-acute and chronic experiments with their duration being up to 196 days and single clinical observations revealed a number of both toxic and non-toxic effects. Organic NC modifiers were highly toxic in vitro. Besides, NC produce anti-microbe effects and it may result in dysbiotic disorders when they are introduced orally. Model experiments revealed that NC and their organic modifiers could possibly migrate from packages into food products. NC are able to free silicon and aluminum that are partly biologically available. A contribution made by NC that are contained in packages into overall exposure to toxic aluminum should be examined profoundly given an adverse situation caused by clay minerals being introduced into a human body as components contained in food additives. Assessment of aluminum consumption with food rations in Russia and several foreign countries revealed it was necessary to exclude potassium and calcium aluminosilicates, bentonite, and kaolin (Е555, Е556, Е558, and Е559) from the list of additives that are permitted for use in food industry.
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- 2020
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27. 大米强化营养素及其生物效能研究进展.
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孟倩楠, 刘畅, 刘晓飞, 杨春瑜, and 张娜
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CHINESE people ,NUTRITIONAL value ,RICE processing ,RICE ,MICRONUTRIENTS - Abstract
Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2021
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28. THE EFFECTS OF VITAMIN B12 DEFICIENCY.
- Author
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KOPRIVICA, Marko, BJELANOVIĆ, Jelena, and VELICKI, Radmila
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- *
VITAMIN B12 deficiency , *VITAMIN B6 , *VITAMIN B12 , *DIETARY supplements , *VITAMIN B deficiency - Abstract
Vitamin B12 is one of the most important B vitamins. This vitamin has an important role in cellular metabolism and is also associated with folate and vitamin B6 metabolism. Vitamin B12 deficiency occurs as a result of some diseases, the use of certain medications, or inadequate nutrition. It primarily affects the elderly and women, but is also common among the pediatric population. The B12 deficiency mostly affects the functions of the nervous and hematopoietic systems but it can also affect the skin, heart, bones, and eyes. The treatment of vitamin B12 deficiency includes oral or intramuscular vitamin B12 supplementation according to different treatment regimens. [ABSTRACT FROM AUTHOR]
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- 2021
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29. Synthesis and Formulation Development of Phenytoin by Inclusion Complexation.
- Author
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AGRAWAL, S., GAIKWAD, SNEHAL, PATEL, RIYA, SHINDE, LEENA, and DESHMUKH, A.
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- *
DRUG solubility , *PHENYTOIN , *ANTICONVULSANTS , *DRUG utilization , *FACTORIAL experiment designs , *BIOAVAILABILITY , *BIOPHARMACEUTICS - Abstract
Phenytoin is a classical anticonvulsant drug used in the treatment of epilepsy. It is a Biopharmaceutics classification system class II drug that has poor aqueous solubility, which affects dissolution rate. The main objective of this study was to enhance the dissolution rate of phenytoin and formulate the optimized chewable tablet. The phenytoin sodium was chemically synthesized and its solubility was enhanced with inclusion complexation by the kneading method using beta-cyclodextrin. This results in increased solubility of phenytoin sodium from 0.0150 to 0.0171 g/ml and solubility was found to be directly proportional to concentration beta-cyclodextrin. Further, 22 factorial design was used to optimize phenytoin sodium chewable tablet with enhanced solubility. In vitro evaluations were done for all 12 formulations to find out the optimized formulation. We found the significant increase in the percentage of drug release, at the end of 2 h, for formulation B6 (81.66 %) and C12 (92.76 %). Also, the pre-compressional and post-compressional properties of B6 and C12 formulations were found to be within the acceptable range of chewable tablets. In conclusion, the solubility of phenytoin sodium was enhanced and we successfully developed two (B6 and C12) optimized formulation of phenytoin sodium chewable tablet. [ABSTRACT FROM AUTHOR]
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- 2021
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30. Toxicological and hygienic assessment of titanium dioxide nanoparticles as a component of E171 food additive (review of the literature and metahanalysis)
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I.V. Gmoshinski, O.V. Bagryantseva, and S.A. Khotimchenko
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titanium dioxide ,food additive ,nanoparticles ,exposure ,biological availability ,toxicity ,intestinal microbiocenosis ,risks ,Medicine - Abstract
The review focuses on exposure values, biological availability, toxic effects, and risks caused by nanoparticles of TiO2 under their oral introduction into a body as a food coloring agent or E171 food additive, or as a significant component in its structure. According to toxicological assessment performed by JECFA in 1969, TiO2 is considered to be insignificantly hazardous. However, at present experts employed by several foreign and international organizations that deal with food safety believe that the assessment should be reviewed as there are new scientific data on adverse effects produced by nano-sized TiO2 on a human body. Overall intake of TiO2 by people with food products, cosmetics (tooth pastes) and medications can vary from 0.5 to 5 mg a day; children aged 3–9 and teenagers aged 10–17 are the most exposed population groups. Despite insignificant intestinal absorption of TiO2 nano- and micro-sized particles, a lot of scientific works revealed their overall toxic effects produced on a body under oral and intragastric introduction. Detected effects produced by TiO2 include organotoxic (mostly hepatotoxic) ones, genotoxicity, immune toxicity, reproductive toxicity, and neurotoxicity. Still, there haven't been any data on carcinogenic effects produced by TiO2 when it is introduced into the gastrointestinal tract. Presumably, some effects produced by TiO2 nanoparticles are mediated by their local impacts on the lymphoid tissue associated with an intestinal mucosa as well as on the structure and activity of intestinal microbiocenosis, and nanoparticles are not necessarily absorbed in the intestines in the process. We performed meta-analysis of 64 articles (published over 2007–2019) which complied with criteria related to scientific authenticity and completeness; the meta-analysis revealed that a probable NOAEL for nano-sized TiO2 amounted to less than 10 mg/kg of body weight a day, and a daily reference safe dose of the substance is estimated as being equal to 0.1 mg/kg of body weight. Given all the above-mentioned, a risk caused by TiO2 intake as E171 food additive depends on nanoparticles fracture in its composition and it can be unacceptably high if this fracture exceeds 10 % of the overall TiO2 mass. Therefore, it is necessary to control and regulate TiO2 nanoparticles contents in the structure of E171 food additive that is applied in food industry.
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- 2019
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31. Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids
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Mahdi Hatamipour, Amirhossein Sahebkar, Seyedeh Hoda Alavizadeh, Mahyar Dorri, and Mahmoud Reza Jaafari
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Biological availability ,Curcuminoid ,Drug stability ,Micelle ,Pharmacokinetics ,Medicine - Abstract
Objective(s): Curcuminoids, comprising curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), are bioactive phytochemicals with numerous pharmacological effects. Oral biological availability of curcuminoids is low due to the low aqueous solubility and rapid metabolism. This study aimed at fabricating a nanomicellar curcuminoid formula with enhanced pharmacokinetic properties. Materials and Methods: Curcuminoids nanomicelles were prepared and characterized regarding particle properties, stability, release profile and pharmacokinetic parameters.Results: Encapsulation efficiency of curcuminoids in nanomicelles were 100%. Particle size analysis demonstrated a mean size of around 10 nm that remained stable for 24 months. Dissolution test showed the complete dissolution of encapsulated curcuminoids from nanomicelles within 20 min while the free curcuminoids were poorly dissolved (approximately 7% after 60 min). The results of long-term (24 months) and accelerated (6 months) stability studies showed no changes in the size and content of nanomicelles. The release studies in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) showed no release of curcuminoids for at least 4 hours. In vivo study in BALB/c mice showed improved pharmacokinetic parameters including maximum plasma concentration (Cmax) and time to reach the maximum concentration (Tmax) with nanomicelles as compared to free curcuminoids and two other commercial products. Tmax for all the three curcuminoid components was observed 30 min following oral administration. AUC of nanomicellar curcuminoids was 59.2 times more than free curcuminoids. Conclusion: These data indicated that nanomicelles could improve solubility, oral bioavailability and also the stability of curcuminoids. Thus, they merit further investigation for enhancing pharmacological effects of curcuminoids.
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- 2019
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32. Вплив складу супрамолекулярних комплексів зостеран–борна кислота на ефективність ростових процесів злакових культур
- Author
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Serhii Prymachenko, Antonina Kustovska, and Denys Mokhniev
- Subjects
Biological activity ,Biological availability ,Complex compounds ,Supramolecular complexes ,Boric acid ,Pectin ,Zosteran ,Biology (General) ,QH301-705.5 - Abstract
Проблематика. Бор визнаний важливим мікроелементом для процесів функціонування вищих рослин. Роль бору специфічна – він є незамінним елементом живлення, без якого життєдіяльність рослин неможлива. Основним джерелом бору для живлення рослин є борна кислота, яка в ґрунтовому розчині перебуває у вигляді недисоційованих молекул і характеризується досить низькою розчинністю та біодоступністю. Для транспортування борної кислоти в рослину може бути використаний пектин, що утворює з борною кислотою комплекси з молярним співвідношенням 1:1 і 2:1. Визначення біодоступності кожного з цих комплексів дасть можливість оптимізувати процес введення борвмісних добрив. Мета. Введення бору в рослини у формі супрамолекулярних комплексів борної кислоти з пектином для дослідження біоактивності таких комплексів залежно від їх складу. Методика реалізації. Пектин екстрагували з листя гідробіонта Зостери морської (Zostera marina). Ареал поширення цієї вищої рослини в Україні – узбережжя Чорного моря Одеської області. Об’єктами дослідження впливу біологічної активності зостеран-борних супрамолекулярних комплексів на функції росту кореневої та наземної частин були використані тест-культури кукурудзи та пшениці. Маса кореневої системи і наземної частини рослини вимірювалася за оригінальною методикою через 96 год після закладення експерименту (24 год замочування насіння в дистильованій воді та 72 год у розчині супрамолекулярного комплексу зостеран–борна кислота). Результати. У результаті пророщування насіння на розчинах супрамолекулярних комплексів різного складу було виявлено, що на ростові процеси наземної частини рослин комплекси чинять значний активуючий вплив. Показано, що біологічна активність розчинів суттєво залежить від природи культури. Кукурудза показала більш високу загальну біологічну активність супрамолекулярних комплексів (до 108 %) порівняно з пшеницею (60 %). При цьому розчин супрамолекулярного комплексу зостеран–борна кислота у мольному співвідношенні 1:1 виявився ефективним для обох культур. Комплекси зостеран–борна кислота в мольному співвідношенні 2:1 не показали високої біологічної активності. Висновки. Високу біологічну активність (107,87 % для кукурудзи і 60,35 % для пшениці) показав комплекс із масовим співвідношенням зостеран–борна кислота 1:20. За такого масового співвідношення найбільш імовірне утворення комплексів зостеран–борна кислота з молярним співвідношенням 1:1, що пов’язано з меншими розмірами і тому більшою біодоступністю таких комплексів. Комплекси пектин–борна кислота 2:1 показали нижчу біологічну активність (103,33 % для кукурудзи і 11,18 % для пшениці), що можна пояснити стеричними обмеженнями при проникненні їх у рослину.
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- 2019
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33. Pharmacokinetics of a high-concentration formulation of buprenorphine (Simbadol) in male dogs.
- Author
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Hansford, Jeremy, Henao-Guerrero, Natalia, Machado, Marcela L., and Pypendop, Bruno H.
- Subjects
- *
BEAGLE (Dog breed) , *LIQUID chromatography-mass spectrometry , *BUPRENORPHINE , *PHARMACOKINETICS , *DOGS - Abstract
To describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine. Prospective, randomized, crossover study. A total of six healthy male intact Beagle dogs, aged 9–13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation). Dogs were randomized to be administered buprenorphine (0.12 mg kg–1; Simbadol, 1.8 mg mL–1) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography–tandem mass spectrometry. A three-compartment model with zero or biphasic rapid and slow first-order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first-order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg–1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute–1 kg–1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80–239)%. Calculated terminal half-life was 963 minutes. The high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues. [ABSTRACT FROM AUTHOR]
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- 2021
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34. Exploring the effect of vitamin D3 supplementation on surrogate biomarkers of cholesterol absorption and endogenous synthesis in patients with type 2 diabetes—randomized controlled trial.
- Author
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Meng, Huicui, Matthan, Nirupa R, Angellotti, Edith, Pittas, Anastassios G, and Lichtenstein, Alice H
- Subjects
CHOLESTEROL metabolism ,BIOMARKERS ,CHOLESTEROL ,DIETARY supplements ,HIGH density lipoproteins ,LOW density lipoproteins ,TYPE 2 diabetes ,STATISTICAL sampling ,CHOLECALCIFEROL ,RANDOMIZED controlled trials - Abstract
Background Inverse associations have been reported between serum 25-hydroxyvitamin D [25(OH)D] and circulating cholesterol concentrations in observational studies. Postulated mechanisms include reduced bioavailability of intestinal cholesterol and alterations in endogenous cholesterol synthesis. Objective To explore the effect of daily supplementation with 4000 IU/d vitamin D
3 for 24 wk on surrogate biomarkers of cholesterol absorption (campesterol and β-sitosterol) and endogenous synthesis (lathosterol and desmosterol). Methods Ancillary study of The Vitamin D for Established Type 2 Diabetes (DDM2) trial. Patients with established type 2 diabetes (N = 127, 25–75 y, BMI 23–42 kg/m2 ) were randomly assigned to receive either 4000 IU vitamin D3 or placebo daily for 24 wk. Of participants without changes in cholesterol-lowering medications (n = 114), plasma surrogate cholesterol absorption and endogenous synthesis biomarker concentrations were measured and merged with available measures of serum LDL cholesterol and HDL cholesterol concentrations. Results At week 24, vitamin D3 supplementation significantly increased 25(OH)D concentrations (+21.5 ± 13.4 ng/mL) but not insulin secretion rates (primary outcome of the parent study) as reported previously. In this ancillary study there was no significant effect of vitamin D3 supplementation on serum cholesterol profile or surrogate biomarkers of cholesterol absorption and endogenous synthesis. Compared with participants not treated with cholesterol-lowering medications, those who were treated exhibited a greater reduction in plasma campesterol concentrations in the vitamin D3 but not placebo group (P- interaction = 0.011). Analyzing the data on the basis of cholesterol absorption status (hypo- versus hyperabsorbers) or cholesterol synthesis status (hypo- versus hypersynthesizers) did not alter these results. Conclusions Vitamin D3 supplementation for 24 wk had no significant effect on surrogate biomarkers of cholesterol absorption or endogenous synthesis, consistent with the lack of effect on serum cholesterol profile. Vitamin D3 supplementation resulted in greater reduction in campesterol concentrations in participants not using compared with those using cholesterol-lowering medications. Further studies are required. This trial was registered at clinicaltrials.gov as NCT01736865. [ABSTRACT FROM AUTHOR]- Published
- 2020
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35. On biological availability dependent bone remodeling.
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Papastavrou, Areti, Schmidt, Ina, and Steinmann, Paul
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- *
BIOAVAILABILITY , *BONE remodeling , *FINITE element method , *BONE density , *BONES - Abstract
Modeling the evolution of bone density is relevant for understanding, simulation and possible prediction of bone response to external and internal influences. In this work we present a formulation for the bone density evolution process that takes into account not only the commonly considered mechanical stimulus, but, as novelty, also the influence of the availability of nutrients and hormones, with its implementation pursued within the finite element method. A simple uni-axial extension test is used to illustrate and compare our novel model against the classical approach. The results of the proposed modified model are promising for application to real-life problems. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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36. Defining Iron Deficiency in Heart Failure: Importance of Transferrin Saturation.
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Martens, Pieter and Tang, W. H. Wilson
- Published
- 2024
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37. Food Effect Study to Assess the Impact on Edaravone Pharmacokinetic Profiles in Healthy Participants
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Hidetoshi, Shimizu, Yukiko, Nishimura, Youichi, Shiide, Makoto, Akimoto, Hideaki, Matsuda, Yuichiro, Kato, and Manabu, Hirai
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Adult ,Male ,Pharmacology ,Cross-Over Studies ,Biological Availability ,Administration, Oral ,Fasting ,Healthy Volunteers ,Food-Drug Interactions ,Area Under Curve ,Edaravone ,Humans ,Female ,Pharmacology (medical) - Abstract
The safety and efficacy of intravenous edaravone, a neuroprotectant used for the treatment of amyotrophic lateral sclerosis (ALS), have been shown in clinical trials. An oral suspension of edaravone has been developed, but the food effect on its pharmacokinetic profile has not been evaluated. This study aimed to assess the food effect on the pharmacokinetic profile of edaravone after oral administration and to investigate dosing regimens and administration instructions with different meal intake and timing.Data from 3 Phase I clinical studies were used to evaluate the effect of food on the pharmacokinetic profiles of a single dose of edaravone oral suspension. In all 3 studies, participants received a single dose of edaravone with various meal conditions. Healthy Japanese adult male participants (Studies 1, 2, and 3) or female participants (Study 3) aged 20 to 45 years at the time of informed consent were included.In Study 1, 6 participants were enrolled and 5 completed the study. Nine and 16 participants were treated in Studies 2 and 3, respectively, and all completed the study. The COral administration of edaravone with a meal decreased the plasma concentration of edaravone. Oral administration of edaravone 8 hours after a high-fat meal, 4 hours after a low-fat meal, 2 hours after a light meal, and 1 hour before a high-fat meal showed no effect of food on the PK profile of unchanged edaravone compared with that observed under a fasted condition.gov identifiers: NCT04481750, NCT04481789, and NCT05342597.
- Published
- 2022
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38. Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study
- Author
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Francisco Beraldi-Magalhaes, Suzanne L. Parker, Cristina Sanches, Leandro Sousa Garcia, Brenda Karoline Souza Carvalho, Mariana Millan Fachi, Marcus Vinicius de Liz, Roberto Pontarolo, Jeffrey Lipman, Marcelo Cordeiro-Santos, and Jason A. Roberts
- Subjects
tuberculosis ,ethambutol ,pharmacokinetics ,biological availability ,intensive care ,critical care ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Tuberculosis (TB) patients admitted to intensive care units (ICU) have high mortality rates. It is uncertain whether the pharmacokinetics of first-line TB drugs in ICU patients are different from outpatients. This study aims to compare the pharmacokinetics of oral ethambutol in TB patients in ICU versus TB outpatients and to determine whether contemporary dosing regimens achieve therapeutic exposures. Methods: A prospective population pharmacokinetic study of ethambutol was performed in Amazonas State, Brazil. Probability of target attainment was determined using AUC/MIC > 11.9 and Cmax/MIC > 0.48 values. Optimized dosing regimens were simulated at steady state. Results: Ten ICU patients and 20 outpatients were recruited. Ethambutol pharmacokinetics were best described using a two-compartment model with first-order oral absorption. Neither ICU patients nor outpatients consistently achieved optimal ethambutol exposures. The absorption rate for ethambutol was 2-times higher in ICU patients (p < 0.05). Mean bioavailability for ICU patients was >5-times higher than outpatients (p < 0.0001). Clearance and volume of distribution were 93% (p < 0.0001) and 53% (p = 0.002) lower in ICU patients, respectively. Conclusions: ICU patients displayed significantly different pharmacokinetics for an oral fixed-dose combination administration of ethambutol compared to outpatients, and neither patient group consistently achieved pre-defined therapeutic exposures.
- Published
- 2021
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39. Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1
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Laura Foucault-Fruchard, Claire Tronel, Sylvie Bodard, Zuhal Gulhan, Julie Busson, Sylvie Chalon, and Daniel Antier
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nerve regeneration ,curcumin ,Alzheimer′s disease ,senile dementia ,early diagnosis ,positron emission tomography ,magnetic resonance imaging ,biological availability ,chemical components ,neurodegeneration ,neural regeneration ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR) activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1), the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.
- Published
- 2018
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40. Use of curcumin in diagnosis, prevention, and treatment of Alzheimer's disease
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Min Chen, Zhi-Yun Du, Xi Zheng, Dong-Li Li, Ren-Ping Zhou, and Kun Zhang
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nerve regeneration ,curcumin ,Alzheimer′s disease ,senile dementia ,early diagnosis ,positron emission tomography ,magnetic resonance imaging ,biological availability ,chemical components ,neurodegeneration ,neural regeneration ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
This review summarizes and describes the use of curcumin in diagnosis, prevention, and treatment of Alzheimer's disease. For diagnosis of Alzheimer's disease, amyloid-β and highly phosphorylated tau protein are the major biomarkers. Curcumin was developed as an early diagnostic probe based on its natural fluorescence and high binding affinity to amyloid-β. Because of its multi-target effects, curcumin has protective and preventive effects on many chronic diseases such as cerebrovascular disease, hypertension, and hyperlipidemia. For prevention and treatment of Alzheimer's disease, curcumin has been shown to effectively maintain the normal structure and function of cerebral vessels, mitochondria, and synapses, reduce risk factors for a variety of chronic diseases, and decrease the risk of Alzheimer's disease. The effect of curcumin on Alzheimer's disease involves multiple signaling pathways: anti-amyloid and metal iron chelating properties, antioxidation and anti-inflammatory activities. Indeed, there is a scientific basis for the rational application of curcumin in prevention and treatment of Alzheimer's disease.
- Published
- 2018
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41. Nano-technological methods for increasing the oral bioavailability of curcumin
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Razieh Nazari, Naghmeh Sattarahmady, and Hossein Heli
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Curcumin ,Biological Availability ,drug delivery ,Nanotechnology ,Medicine (General) ,R5-920 - Abstract
Background & Objective: Curcumin is a tropical plant in the ginger (Zingiberaceae) family. Three curcuminoids were from turmeric: Curcumin, demethoxycurcumin, and Bisdemethoxycurcumin. The potential health benefits of curcumin are limited by their poor solubility, hydrophobic property, and low absorption from the gut, rapid metabolism and rapid systemic elimination. Materials & Methods: Scholarly articles were selected using valid keywords and searching on the SID, Google Scholar, PubMed and Elsevier databases. The aim of this paper is to introduce Nano-technological techniques for increasing the oral bioavailability of curcumin. Results: Increase in the drug bioavailability is one of the goals of nanotechnology. Nano-scale materials increase the drug bioavailability due to their unique features. The bioavailability of a drug is defined as a percentage of the initial dose that is independent of the administration route of the drug entering the bloodstream. To improve the bioavailability of curcumin, numerous techniques are used such as curcumin liposome complex, curcumin phospholipid nanoparticles and structural analogues of curcumin. Conclusion: Curcumin has a unique biological and pharmaceutical property. Of course, one of the major limitations of curcumin is its instability and its low solubility. Thus, it is useful to provide a method that can increase the solubility of poorly soluble drugs in water and protect them to achieve the target site. Nanotechnology has provided many ways to improve the solubility and transport of these drugs.
- Published
- 2017
42. Pharmacokinetics of Morphine Sulfate Orodispersible Tablets and Bioequivalence with Immediate-Release Oral Morphine Sulfate Formulations in Healthy Adult Subjects Under Fasting Conditions: Single-Dose Comparative Bioavailability Studies
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Nicolas Atrux-Tallau, Zulaikha Naimi, and Eric-Olivier Jaudinot
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Adult ,Cross-Over Studies ,Morphine ,Sulfates ,Administration, Oral ,Biological Availability ,Pain ,Fasting ,General Medicine ,Therapeutic Equivalency ,Area Under Curve ,Humans ,Pharmacology (medical) ,Child ,Aged ,Tablets - Abstract
An orodispersible tablet (ODT) formulation of morphine sulfate has been developed to provide a novel alternative for patients with severe pain requiring opioids. This formulation has been developed in a range of doses (1-30 mg), enabling relief from severe pain to be achieved and maintained with the lowest possible morphine dose for each patient. The ODT formulation is particularly suitable for patients with swallowing difficulties.The aim of this study was to compare the pharmacokinetics and bioequivalence of the ODTs with reference formulations of morphine sulfate.Three randomized, single-dose, laboratory-blinded, phase I, crossover studies were conducted in adult healthy volunteers under fasting conditions. The pharmacokinetics of a 30 mg morphine sulfate ODT were compared with those of equivalent doses of currently marketed oral immediate-release formulations: tablets (SevredolA total of 104 subjects were included across the three studies. The pharmacokinetics of the ODTs were assessed in 100 subjects and were found to be similar to those of the reference formulations. The time to maximum plasma concentration (TThe ODTs were safe, well tolerated, and showed similar pharmacokinetics to those of the reference formulations. The development of a range of doses of morphine sulfate ODTs may provide a new alternative for the oral administration of immediate-release morphine for pain management in pediatric, geriatric and adult populations with swallowing problems.
- Published
- 2022
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43. Advances in Nanoformulated Polyphenols for Protection Against Cardiovascular Diseases
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Prasanti, Sharma and Neelima, Sharma
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Pharmacology ,Drug Delivery Systems ,Cardiovascular Diseases ,Animals ,Polyphenols ,Nanoparticles ,Biological Availability ,Cardiology and Cardiovascular Medicine - Abstract
In the past decade, a plethora of research has revealed numerous biological effects of polyphenols, most significantly anticancer and antimicrobial. These versatile, naturally occurring compounds have attracted growing interest among researchers owing to their crucial role in modifying disease progression associated with almost all the body's vital systems, including cardiovascular, neurological, and gastrointestinal systems. However, poor water solubility and rapid metabolism result in low bioavailability, which is a critical limitation to their clinical use. Nanotechnology is one promising approach that has served to maximize the therapeutic potential of polyphenols. Incorporation of sensitive polyphenolic compounds into nanocarriers protects them from physiological degradation, facilitates prolonged release, improves bioavailability, and allows targeted drug delivery. There is emerging evidence that nanomedicine could provide a solution to the poor pharmacokinetics of polyphenols and enhance their treatment efficacy. This review focuses on the various nanoparticle-based delivery systems that have been developed for the entrapment of these hydrophobic molecules and circumvent the pitfalls of poor systemic availability with an emphasis on their application in cardiovascular disorders. It elucidates recent developments in nanotechnology that could not only be imperative to cardiovascular disease alleviation but also in resolving issues of safety and specificity associated with these molecules. It also highlights the improved physicochemical properties and possible molecular mechanisms of some major polyphenols administered as nanoformulations and describes the results of in vitro and in vivo studies performed in animal models of cardiovascular diseases (CVDs).
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- 2022
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44. Novel Mucoadhesive Chitosomes as a Platform for Enhanced Oral Bioavailability of Cinnarizine
- Author
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Hagar Ahmed Oransa, Mariza Fouad Boughdady, and Hassan Mohamed EL-Sabbagh
- Subjects
Chitosan ,Organic Chemistry ,Biophysics ,Biological Availability ,Pharmaceutical Science ,Bioengineering ,General Medicine ,Cinnarizine ,Biomaterials ,International Journal of Nanomedicine ,Liposomes ,Drug Discovery ,Humans ,Caco-2 Cells - Abstract
Hagar Ahmed Oransa, Mariza Fouad Boughdady, Hassan Mohamed EL-Sabbagh Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia, EgyptCorrespondence: Hagar Ahmed Oransa, Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, El-Gomhoria Street, Mansoura, Dakahlia, Egypt, Tel +201065838485, Fax +20502247496, Email hagar_ahmed_93@mans.edu.egPurpose: Cinnarizine (CIN) is a class II BSC drug, suffering from erratic bioavailability due to its pH-dependent solubility. It has preferential absorption in the stomach. In this study, new chitosan (CS) coated niosomes of CIN (CIN-loaded chitosomes) have been developed to extend the gastric retention and ameliorate CIN oral bioavailability.Methods: Various CIN-loaded niosomes were fabricated by thin-film hydration technique and fully characterized. Based on the predetermined criteria of low particle size (PS) and high entrapment efficiency percent (EE%), niosomal formulation F1 was selected and further coated with different CS concentrations. The optimized chitosomal formulation (C2) was evaluated through solid state characterization and mucoadhesive efficiency testing. It was also subjected to cytotoxicity study on Caco-2 cells; besides, in vitro drug release, stability and pharmacokinetic studies were assessed.Results: The optimized chitosomal formulation (C2) exhibited an EE% of 58.30± 2.75%, PS of 440 ± 13.03 nm, PDI of 0.335± 0.21 and ZP of +28.1± 0.10 mv. Solid state characterization results revealed the compatibility between the vesicle components and the entrapment of CIN within niosomal vesicles. C2 formulation demonstrated favorable mucoadhesive efficiency. The cytotoxicity study on Caco-2 cells manifested the safety of the optimized chitosomal formulation (C2) over the free drug. Additionally, it displayed a remarkable sustaining of CIN in vitro release up to 8 h and exhibited a good stability at the refrigerated temperature up to 3 months. In vivo pharmacokinetic assessment revealed that the CIN bioavailability from the optimized chitosomal formulation C2 was enhanced by 2.79 and 1.92 folds compared to the free drug and uncoated niosomal formulation F1, respectively. The priority of the chitosomal formulation (C2) over the niosomal one (F1) was also conferred.Conclusion: Novel formulation of chitosan coated niosomes (chitosomes) could be presented as a promising platform to improve the oral bioavailability of drugs with narrow absorption window.Keywords: cinnarizine, niosome, chitosan, mucoadhesion
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- 2022
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45. Advanced research on extracellular vesicles based oral drug delivery systems
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Mengdi, Song, Mingxiao, Cui, Zhou, Fang, and Kehai, Liu
- Subjects
Extracellular Vesicles ,Drug Delivery Systems ,Nucleic Acids ,Biological Availability ,Administration, Oral ,Pharmaceutical Science - Abstract
The oral route is the most convenient and simplest mode of administration. Nevertheless, orally administration of some commonly used therapeutic drugs, such as polypeptides, therapeutic proteins, small-molecule drugs, and nucleic acids, remains a major challenge due to the harsh gastrointestinal environment and the limited oral bioavailability. Extracellular vesicles (EVs) are diverse, nanoscale phospholipid vesicles that are actively released by cells and play crucial roles in intercellular communications. Some EVs have been shown to survive with the gastrointestinal tract (GIT) and can cross biological barriers. The potential of EVs to cross the GIT barrier makes them promising natural delivery carriers for orally administered drugs. Here, we introduce the uniqueness of EVs and their feasibility as oral drug delivery vehicles (ODDVs). Then we provide a general description of the different cellular EVs based oral drug delivery systems (ODDSs) currently under study and emphasize the contribution of endogenous features and multifunctional properties of EVs to the delivery performance. The current obstacles of moving EVs based ODDSs from bench to bedside are also discussed.
- Published
- 2022
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46. Fabrication of an aprepitant nanosuspension using hydroxypropyl chitosan to increase the bioavailability
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Jinwen, Liu, Shuyan, Li, Wuliji, Ao, Yongji, Li, Yingge, Xiao, and Meirong, Bai
- Subjects
Chitosan ,Biophysics ,Administration, Oral ,Biological Availability ,Water ,Cell Biology ,Biochemistry ,Solubility ,Suspensions ,Humans ,Nanoparticles ,Caco-2 Cells ,Particle Size ,Molecular Biology ,Aprepitant - Abstract
Aprepitant has been classified into BCS class IV, which has low permeability and poor water solubility, resulting in low bioavailability. This study focused on improving its permeability and solubility in order to improve the oral bioavailability of aprepitant. Hydroxypropyl chitosan (HPCS) was used as a stabilizer for the nanosuspension and wet milling was utilized for improving aprepitant's bioavailability and solubility. The resulting nanosuspension size was 151 ± 14.5 nm and its zeta potential was 63.5 ± 0.34 Mv. The spectral characteristics (XRPD, DSC, TEM) of the nanosuspension suggested that aprepitant existed in the crystalline form and that nanosuspension had 2-fold higher solubility than aprepitant. Hydroxypropyl chitosan can significantly reduce the TEER of Caco-2 cells and the Psubapp/subof the suspension in Caco-2 cells increased by 2.2 times compared with aprepitant. The relative bioavailability of the nanosuspension was 147.7% compared with the commercial capsule.
- Published
- 2022
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47. Interference of Glucose Bioavailability of Tumor by Engineered Biohybrids for Potentiating Targeting and Uptake of Antitumor Nanodrugs
- Author
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Jia-Wei Wang, Qi-Wen Chen, Guo-Feng Luo, Ping Ji, Zi-Yi Han, Wen-Fang Song, Wei-Hai Chen, and Xian-Zheng Zhang
- Subjects
Glucose ,Paclitaxel ,Neoplasms ,Mechanical Engineering ,Escherichia coli ,Humans ,Biological Availability ,Nanoparticles ,General Materials Science ,Bioengineering ,General Chemistry ,Condensed Matter Physics ,Escherichia coli Infections - Abstract
The chemotherapy efficacy of nanodrugs is restricted by poor tumor targeting and uptake. Here, an engineered biohybrid living material (designated as EcN@HPB) is constructed by integrating paclitaxel and BAY-876 bound human serum albumin nanodrugs (HPB) with
- Published
- 2022
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48. Photodegradation Kinetics and Deep Learning-Based Intelligent Colorimetric Method for Bioavailability-Based Dissolved Iron Speciation
- Author
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Jiayi Luo, Zhaojing Huang, Shunxing Li, Fengying Zheng, Fengjiao Liu, Qianyan Huang, Xuguang Huang, and Haijiao Xie
- Subjects
Photolysis ,Deep Learning ,Iron ,Biological Availability ,Colorimetry ,Analytical Chemistry - Abstract
Via the photodegradation of dissolved iron (dFe) complexes in the euphotic zone, released free Fe(III) is the most important source of bioavailable iron for eukaryotic phytoplankton. There is an urgent need to establish bioavailability-based dissolved iron speciation (BDIS) methods. Herein, an intelligent system with dFe pretreatment and a colorimetric sensor is developed for real-time monitoring of newly generated Fe(III) ions. According to the photodegradation kinetics of dFe, including kinetic constant and photogenerated time of free Fe(III) ions, 3 sources, 6 kinds, and 12 species of dFe are determined by our photocatalytic-assisted colorimetric sensor and deep learning model within 20.0 min. The algal dFe-uptake for 4 days can be predicted by BDIS with correlation coefficient 0.85, which could be explained by the hard and soft acids and bases theory (HSAB) and density functional theory (DFT). These results successfully demonstrate the proof-of-concept for photodegradation kinetics-based speciation and bioavailability assessments of dissolved metals.
- Published
- 2022
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49. Effect of Food on the Pharmacokinetics of Senaparib (IMP4297) in Healthy Chinese Subjects
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Xianmin, Meng, Xiaoyan, Lin, Rongrong, Jiang, Yan, Lu, Liyan, Zeng, Ming, Cao, and Jianliang, Zhang
- Subjects
Male ,Food-Drug Interactions ,China ,Cross-Over Studies ,Area Under Curve ,Humans ,Administration, Oral ,Biological Availability ,Pharmacology (medical) ,General Medicine ,Healthy Volunteers - Abstract
Data on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects.This is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study.Sixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration-time curve from time zero to the last measurable concentration and area under the plasma concentration-time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported.Food slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food.ClinicalTrials.gov NCT04057729.
- Published
- 2022
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50. Successful Conversion of Pb-Contaminated Soils to Low-Bioaccessibility Plumbojarosite Using Potassium-Jarosite at Ambient Temperature
- Author
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Tyler D. Sowers, Matthew D. Blackmon, Sharon E. Bone, Alicia M. Kirby, Marissa L. Jerden, Matthew R. Noerpel, Kirk G. Scheckel, and Karen D. Bradham
- Subjects
Soil ,Minerals ,Lead ,Potassium ,Temperature ,Soil Pollutants ,Biological Availability ,Environmental Chemistry ,General Chemistry - Abstract
Methods promoting lead (Pb) phase transformation in soils are essential for decreasing Pb bioaccessibility/bioavailability and may offer an in situ, cost-efficient process for mitigating contaminant exposure. Recent plumbojarosite (PLJ) conversion methods have shown the greatest potential to reduce soil Pb bioaccessibility, an in vitro bioaccessibility assay measurement of the proportion of Pb solubilized under gastric chemical conditions. Soils tested utilizing the recent PLJ method were found to have a Pb bioaccessibility of1%, compared to original soils possessing bioaccessibility of70%. However, this technique requires heat (95-100 °C) to promote mineral transformation. Jarosite-group minerals may incorporate multiple interlayer cations; therefore, we probed the potential for jarosite to remediate Pb via intercalation by reacting presynthesized potassium (K)-jarosite with aqueous Pb and/or Pb-contaminated soil at room temperature. Both K-jarosite and heated PLJ-treated samples were investigated by pairing bioaccessibility analyses with advanced bulk and spatially resolved X-ray absorption spectroscopy analyses. Samples treated with K-jarosite promoted Pb transformation to low-bioaccessibility (10%) PLJ, with soil being converted to 100% PLJ using both heated and nonheated techniques. μ-X-ray fluorescence (μ-XRF) and μ-X-ray absorption near-edge structure (μ-XANES) showcase significant differences between elemental interactions for heated and nonheated PLJ-treated samples with anglesite impurities being found on the microscale. Although further development is necessary to accommodate for suitable field conditions, results indicate, for the first time, that K-jarosite may successfully convert soil Pb to PLJ without high-temperature conditions. The newfound utility of K-jarosite is expected to be key to future jarosite-based soil Pb remediation method development.
- Published
- 2022
- Full Text
- View/download PDF
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