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Introduction: Miltefosine is a new drug that was recently approved for the treatment of tegumentary leishmaniasis (TL) by the Brazilian health system. It has a teratogenic potential and requires follow-up of patients undergoing treatment. Improving compliance with best practices is essential to ensure the safe and appropriate use of this drug. Objective: This project aimed to implement best practices for the safe and appropriate use of miltefosine in the treatment of TL in the state of Minas Gerais, Brazil. Methods: This project was guided by the JBI Evidence Implementation Framework. Five best practice criteria were established based on the best available evidence. A baseline audit was conducted to measure current practice against best practice. Barriers to best practice were then identified and a follow-up audit was conducted to evaluate changes after the implementation of improvement strategies. Two sites were analyzed: a leishmaniasis reference service in Belo Horizonte, the capital of Minas Gerais, and 28 regional offices. Results: The baseline audit evaluated data from 197 miltefosine requests distributed across 13 regional sites. All requests from the reference service were compliant (100%). This is in contrast to the 60% compliance rate at the regional offices. The improvement strategies included intensifying direct communication with the regional health professionals, which increased the average compliance rate to 79.5%, 6 months after the interventions were introduced. Conclusion: This best practice implementation project effectively increased the compliance rate for the audited procedures. Communication from the reference site with the regional health professionals successfully increased compliance with best practices and promoted the safe and appropriate use of miltefosine. These strategies should analyzed and applied to improve other programs. http://links.lww.com/IJEBH/A184 [ABSTRACT FROM AUTHOR]

Daptomycin, an anti‐methicillin‐resistant Staphylococcus aureus drug, causes exposure‐dependent muscle toxicity and eosinophilic pneumonia. Although the area under the concentration‐time curve (AUC)‐guided dosing is crucial, an optimal blood sampling strategy is lacking. This study aimed to identify an optimal limited sampling strategy using Bayesian forecasting to rapidly achieve the target AUC. Two validated population pharmacokinetic models generated a virtual population of 1000 individuals (models 1 and 2 represent diverse patients and kidney transplant recipients, respectively). The AUC for each blood sample was assessed using the probability of achieving the estimated/reference AUC ratio on the second day (AUC24–48) and at the steady state (AUCss). In Model 1, Bayesian posterior probabilities for AUC24–48 increased from 50.7% (a priori) to 59.4% and for AUCss from 48.9% (a priori) to 61.9%, with one‐point Ctrough sampling at 24 h. With two‐point sampling at 7 and 24 h, the probabilities increased to 73.8% for AUC24–48 and 69.7% for AUCss. In Model 2, the probabilities for both AUC24–48 and AUCss with one‐point Ctrough or two‐point sampling incorporating Ctrough sampling increased compared to a priori probabilities. These results suggest that two‐point sampling incorporating Ctrough during initial dosing enhanced achieving the target AUC24–48 and AUCss rapidly. [ABSTRACT FROM AUTHOR]

Background: Changes in gastrointestinal physiology following bariatric surgery may affect the pharmacokinetics of drugs. Data on the impact of bariatric surgery on drugs used for attention‐deficit/hyperactivity disorder (ADHD) are limited. Methods: In patients treated with ADHD medication and undergoing bariatric surgery, serial drug concentrations were measured for 24 h preoperatively and one, six and 12 months postoperatively. Primary outcome was change in area under the concentration‐time curve from 0 to 24 h (AUC0–24), with other pharmacokinetic variables as secondary outcomes. Results: Eight patients treated with lisdexamphetamine (n = 4), dexamphetamine (n = 1), methylphenidate (n = 1) and atomoxetine (n = 2) were included. In total, 409 samples were analysed. Patients underwent sleeve gastrectomy (n = 5) and Roux‐en‐Y gastric bypass (n = 3). AUC0–24 and Cmax of dexamphetamine increased after surgery in those using the prodrug lisdexamphetamine. There was no clear‐cut reduction in tmax postoperatively. For ritalinic acid and atomoxetine, no changes in AUC0–24 were observed, but for atomoxetine, a higher Cmax and a shorter tmax were observed postoperatively. Conclusion: Bariatric surgery may increase the systemic exposure of dexamphetamine after intake of lisdexamphetamine. Patients using lisdexamphetamine should be followed with regard to adverse drug reactions after bariatric surgery, and, if available, therapeutic drug monitoring should be considered. [ABSTRACT FROM AUTHOR]

Context.--Fondaparinux monitoring is not required among noncritically ill patients due to a predictable doseresponse effect. However, this is debatable among critically ill patients, because fondaparinux bioavailability can be influenced by complicated medical conditions. Objective.--To investigate fondaparinux monitoring among the critically ill. Design.--Retrospective analysis of patients admitted in intensive care unit from February 2021 to December 2021 who received prophylactic fondaparinux and had anti-Xa activity tests. Results.--Of 156 anti-Xa values, 86 (55.1%) were within 0.10--0.50 lg/mL (the recommended prophylactic range), 38 (24.4%) were less than 0.10 lg/mL, and 32 (20.5%) were greater than 0.50 lg/mL, demonstrating an unpredictable dose-response effect. Among 70 patients, thrombotic tendency was controlled in 32 (45.7%), thrombosis progressed in 22 (31.4%), and bleeding events occurred in 16 (22.9%). Patients with progressed thrombosis had 17 of 54 (31.5%) anti-Xa values less than 0.10 lg/mL; even though this proportion was greater than that of patients with controlled thrombotic tendency (11 of 72, 15.3%), it was similar to that of patients with bleeding (10 of 30, 33.3%), indicating a weak practicability of anti-Xa for monitoring fondaparinux efficacy. Thrombin-antithrombin complex showed a gradual decline among patients with controlled thrombotic tendency but a bounce-back effect among patients with progressed thrombosis. Thrombelastography R value above the upper reference value occurred more frequently among patients with bleeding (4 of 6, 66.7%) compared to patients without bleeding (4 of 22, 18.2%) (P ¼ .01). Conclusions.--The fondaparinux dose-response effect was unpredictable among the critically ill; anti-Xa activity combined with thrombin-antithrombin complex and thrombelastography can be helpful to guide a precise fondaparinux therapy in this population. [ABSTRACT FROM AUTHOR]

Context.--New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce. Objective.--To develop and validate a liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy. Design.--Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on an Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiplereaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed. Results.--The method was linear with limit of detection less than 0.05 lg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within 615% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53%(244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals for all 6 ASMs. Conclusions.--A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. These large-scale TDM data could help establish an effective monitoring strategy for these drugs. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, focusing on three key aspects. First, we discuss the importance of drug concentration management for enhancing efficacy while preventing toxicity, considering various patient populations, including pediatric and elderly patients with their unique physiological characteristics. Second, we analyze different PK modeling approaches: the classic top-down approach exemplified by population PK analysis, the bottom-up approach represented by physiologically based PK modeling, and hybrid models combining both approaches for enhanced predictive performance. Third, we explore clinical applications, including nomogram-based dosing strategies, Bayesian estimation, and emerging artificial intelligence applications, for real-time dose optimization. Critical challenges in implementing PK/PD simulation are addressed, particularly the selection of appropriate PK models, the optimization of PK/PD indices, and considerations concerning antimicrobial concentrations at infection sites. Understanding these principles and challenges is crucial for optimizing antimicrobial therapy and combating AMR through improved dosing strategies. [ABSTRACT FROM AUTHOR]

Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Methods: Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. Results: A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. Conclusions: This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vancomycin is a reserve antibiotic that is frequently prescribed for central venous catheter (CVC)-associated infections in hemodialysis patients. Hemodialysis patients are very fragile patients and the presence of CVCs increases the risk of sepsis. We conducted a prospective study, evaluating the needs of changes in vancomycin dosing for treatment based on the use of the new 2020 vancomycin dosing guidelines, to increase drug safety (preventing subtherapeutic or supratherapeutic doses and offering therapeutic concentrations of the drug) in a particular group of patients with sepsis caused by catheter infections and being on intermittent hemodialysis. Methods: This prospective study included patients with sepsis caused by catheter infections and being on intermittent hemodialysis, treated with vancomycin, admitted in the nephrology department and intensive care unit (ICU). Vancomycin levels were adjusted according to the 2020 vancomycin guidelines. Results: In our study, nine (45%) patients had a vancomycin AUC between 400 and 600 mcg × h/mL, five (25%) patients had a subtherapeutic AUC, and six (30%) patients had a supratherapeutic AUC. It is important to mention that in 10 (50%) of the patients included in the study, the loading and maintenance doses mentioned in the protocol were respected, but 50% of them had a supratherapeutic AUC. We observed that a supratherapeutic AUC occurred when the loading dose was 1500 mg or 2000 mg, and in one case at 1000 mg with a low BMI. Conclusions: a therapeutic level of vancomycin can often be difficult to achieve because of different reasons, mainly in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity—where anti-drug antibodies diminish effectiveness—remains an issue, often requiring dose changes or combination therapies. Pharmacogenomics is increasingly applied in IBD to personalise treatment, especially since genetic factors like the HLA-DQA1*05 variant heighten the immunogenicity risk with IFX. This study aims to examine the relationship between the HLA-DQA1*05 variant and response loss or antibody development in patients regularly monitored on IFX or ADA. Methods: Sixty-five paediatric IBD patients were enrolled, with therapeutic drug monitoring (TDM) of IFX and ADA, conducted using immunoenzymatic assays. The presence of the HLA-DQA1*05 T>C allele variant was also tested using a Biomole HLA-DQA1 Real-time PCR kit. Results: The HLA-DQA1*05 rs2097432 T>C allele was present in 54% of patients on IFX and 69% of those on ADA. No statistically significant differences were found between HLA carriers and non-carriers across any of the three analysed groups: IFX, ADA and the overall anti-TNFα. Conclusions: Our study suggests that the HLA-DQA1*05 allele does not increase the risk of secondary loss of response to anti-TNF therapy, likely because most patients were on a combination of anti-TNF agents and immunomodulators, which can lower anti-drug antibody production. Testing for HLA-DQA105 can aid in personalising treatment and optimising therapy to minimise immunogenicity risks. [ABSTRACT FROM AUTHOR]

The goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and N‐acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the model to optimize dosing regimens of cotrimoxazole for Pneumocystis jirovecii pneumonia and in patients with renal insufficiency or with continuous renal replacement therapy (CRRT). This was a retrospective multicenter observational cohort study based on therapeutic drug monitoring (TDM) data from hospitalized patients treated with cotrimoxazole. We developed two population pharmacokinetic (POPPK) models: a model of trimethoprim and an integrated model with both sulfamethoxazole and N‐acetyl sulfamethoxazole concentrations. Monte Carlo simulations were performed to determine the optimal dosing regimen. A total of 348 measurements from 168 patients were available. The estimated glomerular filtration rate (eGFR) and CRRT were included as covariates on the clearance of all three compounds. Cotrimoxazole TID 1,920 mg and b.i.d. 2,400 mg led to sufficient exposure for infections with P. jirovecii in patients without renal insufficiency. To reach equivalent exposure, a dose reduction of 33.3% is needed in patients with an eGFR of 10 mL/minute/1.73 m2 and of 16.7% for an eGFR of 30 mL/minute/1.73 m2. N‐acetyl sulfamethoxazole accumulates in patients with a reduced eGFR. CRRT increased the clearance of sulfamethoxazole, but not trimethoprim or N‐acetyl sulfamethoxazole, compared with the median clearance in the population. Doubling the sulfamethoxazole dose is needed for patients on CRRT to reach equivalent exposure. [ABSTRACT FROM AUTHOR]

Vancomycin, a vital antibiotic for treating gram-positive bacterial infections, requires therapeutic drug monitoring (TDM) because of its substantial pharmacokinetic variability. While traditional TDM relies on steady-state trough concentrations, recent guidelines advocate the area under the concentration-time curve (AUC) as the target index. However, detailed protocols for AUC estimation are lacking, leading to potential discrepancies among institutions. We surveyed medical institutions in Korea regarding vancomycin TDM, including AUC estimation. Nineteen participants responded to the TDM case challenge under three patient scenarios. For an ordinary patient in Case 1, the overall CV for AUC values was 0.4% when both trough and peak concentrations were included in the AUC calculation and 1.9% when utilizing only the trough concentration. For Case 2, an older patient with obesity, the corresponding CV was 6.6%. For Case 3 with multiple trough concentrations, the CV was 15.6%, reflecting variations in the selective use of data. Although the agreements in Case 1 were good, significant variability in AUC estimation was noted in cases involving atypical patient characteristics or old TDM data. Our study provides insight into the current status of vancomycin TDM in Korea and underscores the need for standardized operational protocols for AUC estimation. [ABSTRACT FROM AUTHOR]

Background: We aim to develop a model to predict the probability of tonic-clonic seizures in women with epilepsy (WWE) at any point during pregnancy until six weeks postpartum. Methods: We conducted a screening of patients diagnosed with epilepsy and who were pregnant, at a tertiary hospital in China, during the period of 1 January 2010 to 31 December 2020. We then followed up with these patients for at least one year postpartum. A total of 271 eligible patients were included in the cohort. The outcome was the occurrence of a tonic-clonic seizure during pregnancy or within six weeks postpartum. Predictors were screened through univariate analysis, and models were fitted through multivariate logistic regression analysis. Further, we compared the WMU model with the AntiEpileptic drug Monitoring in PREgnancy (EMPiRE) model in terms of discrimination (the area under receiver operating characteristic curve [AUC]), accuracy (GiViTI calibration belt), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). Finally, we plotted a nomogram of the WMU model. Results: Of the 271 pregnant WWE, 62 patients (22.9%) had the outcome. The WMU model included three predictors: age at the time of pregnancy, admission to hospital for seizures in previous pregnancy, and seizures in the 12 months before pregnancy. Compared to the EMPiRE model, the AUC value of the WMU model was higher (0.76 vs. 0.639, P < 0.05). GiViTI calibration belt showed that the predicted risks of the WMU model were mostly consistent with the observed risks. In terms of DCA, the WMU model revealed the highest net proportional benefit for predicted probability thresholds between 10% and 90%. Additionally, our model exhibited better reclassification performance than the EMPiRE model (NRI: 0.331, P < 0.01 and IDI: 0.129, P < 0.01). Conclusion: We attempted to develop a prognostic model for predicting the risk of tonic-clonic seizures in pregnant WWE. The WMU model showed good performance, but without external validation, it is unclear whether WMU model could be generalized. [ABSTRACT FROM AUTHOR]

AbstractTracking the internalization of non-fluorescent drugs remains a significant challenge in drug delivery systems. Monitoring drug internalization is crucial for enhancing therapeutic efficiency and controlling drug release, minimizing damage to healthy cells. In this study, we synthesized a fluorescent, biocompatible coumarin derivative functionalized with chlorambucil, termed compound 5. The 1,6-heptadiyne moiety, known for its ability to cyclopolymerize in the presence of Hoveyda–Grubbs’ second-generation (HG2) catalyst, was modified with monomethyl poly(ethylene glycol) (mPEG-OH) and compound 5 to create the macromonomer compound 8. This macromonomer was polymerized under inert conditions using HG2, yielding the final polymer, compound 9, with a molecular weight of 21,300 g/mol. All monomer precursors were thoroughly characterized using various analytical techniques. Dynamic light scattering (DLS) revealed a polymer size of 32 nm, while transmission electron microscopy (TEM) showed spherical morphology in a 1 mg/mL solution in deionized water. Compound 9 exhibited promising chemotherapeutic activity against HeLa and MCF-7 cell lines. Further internalization studies demonstrated an increase in fluorescence intensity with increasing polymer concentration in both cell lines. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusions With reports of expanding epidemiology of blastomycosis across the United States, the purpose of this study was to evaluate the incidence and outcomes associated with blastomycosis in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients.We conducted a retrospective case series of adult SOT and HCT recipients at a tertiary care medical center between January 1, 2005 and September 30, 2023. Cases were defined as culture‐proven blastomycosis. We performed descriptive statistical analysis to evaluate diagnosis, management, and outcomes (mortality) of blastomycosis in SOT.The cumulative incidence of blastomycosis was 0.11% with a median time to infection following transplant of 743 days. Of the 19 cases, the majority of patients were SOT recipients (90%). Supratherapeutic immunosuppression within 30 days of diagnosis was observed in 42% of cases with documented drug monitoring. Urine antigen testing was highly sensitive (100%). Fourteen (73.7%) patients received induction therapy with liposomal amphotericin B followed by azole therapy for a minimum of 12 months. Despite appropriate treatment, 1‐year mortality was high at 26.3%, with attributable mortality of 21.1%.While rates of blastomycosis remain low among SOT and HCT recipients, infection is associated with poor posttransplant outcomes. Antigen testing can aid in timely assessment of disease severity and initiation of appropriate therapy. Among survivors, no relapses were observed while on lifelong secondary suppression. Future studies should aim to better define risk factors associated with developing blastomycosis and establish effective strategies for prevention. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) requiring continuous renal replacement therapy is common in critically ill patients. The ADVanced Organ Support (ADVOS) system is a novel hemodialysis machine that uses albumin enriched dialysate which allows the removal of protein-bound toxins and drugs. To date, data on antimicrobial removal under ADVOS has not yet been reported. Methods: An in vitro study was conducted using whole porcine blood and continuous infusions of different antimicrobial agents to investigate the effect of ADVOS on drug exposure. Drugs with varying protein binding, molecular weights and renal clearances, anidulafungin, cefotaxime, daptomycin, fluconazole, ganciclovir, linezolid, meropenem and piperacillin were studied. Results: All studied drugs were removed during the in vitro ADVOS experiment. Clearance under ADVOS (CLADVOS) for low protein-bound drugs, such as cefotaxime, fluconazole, ganciclovir, linezolid, meropenem and piperacillin ranged from 2.74 to 3.4 L/h at a blood flow of 100 mL/min. With a doubling of flow rate CL for these drugs increased. Although efficiently removed, this effect was not seen for CLADVOS in high protein-bound substances such as daptomycin (1.36 L/h) and anidulafungin (0.84 L/h). Conclusion: The ADVOS system effectively removed protein-bound and unbound antimicrobials to a significant extent indicating that dose adjustments are required. Further, clinical studies are necessary to comprehensively assess the impact of ADVOS on antimicrobial drug removal. Until clinical data are available, therapeutic drug monitoring should guide antimicrobial dosing under ADVOS. [ABSTRACT FROM AUTHOR]

Point‐of‐care (POC) monitoring of patient condition is crucial for effective cancer treatment and prognosis. This can be achieved non‐invasively by analyzing exosomes in body fluids. However, the heterogeneity of exosomes and non‐standardized quantification methods may interfere with clearly determining the patient's condition. Therefore, there is a need for technology that can precisely analyze both tumor‐derived exosomes and normal exosomes. Herein, this study presents the exosome multiple‐separation for simultaneous detection (EXO‐MUSSID) platform, which simultaneously isolates different exosomes based on their magnetization properties and monitors therapeutic efficacy of drugs. Using immunoaffinity magnetophoresis technology, HER2‐overexpressing and normal exosomes are collected separately, enabling real‐time monitoring of HER2 (also known as ERBB2) expression by analyzing the mRNA of each exosome based on a catalytic hairpin assembly (CHA) reaction. A portable fluorescence reader customized for the EXO‐MUSSID platform is developed for POC monitoring of HER2‐overexpressing breast cancer (HER2+ BC). The performance of the EXO‐MUSSID platform is validated using urine samples from HER2+ BC mouse models, confirming the progression of HER2+ BC and the changes in HER2 expression due to trastuzumab treatment. It is expected to serve as a valuable tool for exosome‐based liquid biopsy in disease monitoring. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance We aimed to quantify and predict lacosamide exposure during pregnancy by developing a pregnancy physiologically‐based pharmacokinetic model, allowing the prediction of potential dose increases to support maintaining a patient's preconception lacosamide concentrations.Models for nonpregnant adults and pregnant female patients were constructed using physiochemical and pharmacological parameters identified from literature review. Evaluation of plasma concentration data from human males was digitized from the literature. Concentration data in nonpregnant and pregnant human females were available from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a longitudinal observational study which followed 11 nonpregnant and 16 pregnant women receiving lacosamide. Evaluation was conducted qualitatively with visual overlay (>80% of observed concentrations within 90% confidence interval) and quantitatively with average fold error and absolute average fold error (0.8–1.25 ratio acceptance criteria). Simulations of intensively‐sampled dosing regimens at steady‐state dosing across multiple gestational ages were conducted in Simcyp to evaluate the potential changes in lacosamide pharmacokinetics during pregnancy. Additional simulations were performed to explore the effects of cytochrome polymorphisms and glomerular filtration rate variability.The model adequately described the evaluation data in nonpregnant adults and pregnant adults between 10 and 40 weeks of gestation. Estimates in patients at 40‐ weeks of gestation indicated that lacosamide clearance increased by 48.2% compared to nonpregnant patients. Maximum lacosamide concentration (Cmax) during a simulated dosing interval also fell by 30% from preconception to 40 weeks. A simulated dose increase of 50 mg once daily at 10 weeks of gestation supported maintenance of preconception concentration for a typical patient taking the most common dosing regimen of 200 mg, twice daily (BID), preconception.Simulated changes in lacosamide concentration align with the limited data available in observational studies. Our simulations support the use of therapeutic drug monitoring and dose adjustments to maintain the efficacy of lacosamide pharmacotherapy. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant recipients with severe acute respiratory syndrome-coronavirus-2 infection have an increased risk of severe disease and mortality. Nirmaltrevir/ritonavir (Paxlovid) is an effective oral disease-modifying therapy that has been shown to reduce risk of progression to severe disease in high-risk, nonhospitalized adults. However, owing to the potential for serious drug–drug interactions owing to ritonavir-induced inhibition of the CYP3A enzyme, this drug is not suitable option for transplant recipients with mild-moderate severe acute respiratory syndrome-coronavirus-2 infection. Case presentation: A 57-year-old Caucasian man presented to the emergency department with 48 hours of nausea, vomiting, headaches, and lethargy. At 5 days earlier, he was diagnosed with a mild severe acute respiratory syndrome-coronavirus-2 infection by his general practitioner, who commenced treatment with Paxlovid at 300 mg/100 mg twice daily. Past medical history included kidney transplantation in 2018 for end-stage kidney secondary to hypertensive nephrosclerosis, managed with prednisone, tacrolimus, and mycophenolate. Vaccination status was up-to-date and prophylactic tixagevimab/cilgavimab (Evusheld) had been given > 6 months prior owing to lack of seroconversion. Examination showed a blood pressure of 176/94 mmHg and normal respiratory parameters. Investigations demonstrated a serum creatinine of 213 µmol/L (baseline 130 µmol/L) and tacrolimus trough level of 118 µg/L (baseline 6.9–8.7 µg/L). Treatment included intravenous rehydration, Evusheld and tacrolimus were withheld for 7 days, with recommencement guided by regular therapeutic drug monitoring. Conclusion: This acute kidney injury was attributed to tacrolimus toxicity resulting from a drug–drug interaction with Paxlovid. While transplant recipients have an increased risk of severe disease, current Australian guidelines recommend against Paxlovid use in adults taking medications that are heavily dependent on CYP3A4 for clearance, including calcineurin and mammalian target of rapamycin inhibitors. [ABSTRACT FROM AUTHOR]

Background: In the filed of antiviral therapy, effective therapeutic concentration is beneficial to shorten the recovery time of patients and reduce the transmission rate.The aim of this study is to retrospectively analyze the factors that lead to the drug concentration of Nirmatrelvir /Ritonavir (NMV/RTV) not reaching the standard. Methods: In this study, the NMV/RTV drug concentration(Cnmv/rtv) data (n = 114) of COVID-19 patients over 18 years old were collected from May 2022 to July 2022, and the results of the patients were retrospectively compared. According to the analysis of the early study of NMV/RTV, combined with the research results at home and abroad, according to whether the measured drug concentration > 987 ng/ml, the patients were divided into target group and non-target group,The non-target group was defined as not reaching the trough concentration level. Results: Serum NMV/RTV concentration in adult patients was correlated with prognostic nutritional index [PNI, (P < 0.05)], height (P < 0.05), weight (P < 0.05) and creatinine clearance [Crcl, (P < 0.05)]. Multivariate analysis showed that height, weight, PNI, lymphocyte (LYM) and CrCl were independent influencing factors of NMV/RTV trough concentration. However, after the correction of BMI calculation, there was no correlation between NMV/RTV and BMI, so in the clinical medication plan, the drug was not adjusted according to the height and weight. Conclusions: The serum NMV/RTV concentration of adult patients gradually decreased with the increase of CrCl. For patients with high and low CrCl, the trough concentration of NMV/RTV should be continuously monitored and the dosing regimen should be adjusted to achieve the target trough concentration in these patients to reduce the effect of CrCl. PNI is also a key factor affecting drug concentration. For poor nutritional status, drug concentration should be closely monitored and the dose should be adjusted. [ABSTRACT FROM AUTHOR]

AbstractNanomedicine offers a promising avenue for improving retinal drug delivery, effectively addressing challenges associated with ocular diseases like age-related macular degeneration and diabetic retinopathy. Nanoparticles, with their submicron size and customisable surface properties, enable enhanced permeability and retention within retinal tissues, supporting sustained drug release and minimising systemic side effects. Nanostructured scaffolds further provide a supportive environment for retinal cell growth and tissue regeneration, crucial for treating degenerative conditions. Additionally, advanced nanodevices facilitate real-time monitoring and controlled drug release, marking significant progress in retinal therapy. This study reviews recent advancements in nanomedicine for retinal drug delivery, critically analysing design innovations, therapeutic benefits, and limitations of these systems. By advancing nanotechnology integration in ocular therapies, this field holds strong potential for overcoming current barriers, ultimately improving patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Objectives: Exploring adjustments to the voriconazole dosing program based on therapeutic drug monitoring results to implement individualized therapy. Methods: PubMed and Embase were systematically searched to obtain study about voriconazole dose adjustment program guided by therapeutic drug monitoring. Quality evaluation and summarization of the obtained studies were performed to obtain program adjustments for voriconazole under therapeutic drug monitoring. Results: A total of 1,356 and 2,979 studies were searched on PubMed and Embase, respectively, and after removing irrelevant and duplicated studies, a total of 25 studies were included. A loading dose of 5 mg/kg q12 h or 200 mg q12 h and a maintenance dose of 50 mg q12 h or 100 mg q24 h is recommended for patients with Child-Pugh C. And in patients with Child-Pugh C, CYP2C19 genotype had no significant effect on voriconazole blood concentrations. Recommendations for presenting dosing programs based on different CYP2C19 genotypes are inconsistent, and genetic testing is not routinely recommended prior to dosing from a pharmacoeconomic perspective. Additionally, in adult patients, if the voriconazole trough concentration is subtherapeutic, the voriconazole dose should be increased by 25%∼50%. If the voriconazole trough concentration is supratherapeutic,the voriconazole dose should be decreased by 25%∼50%. If a drug-related adverse event occurs, hold 1 dose, decrease subsequent dose by 50%.In pediatric patients, if the voriconazole trough concentration is subtherapeutic, increase the voriconazole dose by 1∼2 mg/kg or increase the voriconazole dose by 50%. If the voriconazole trough concentration is supratherapeutic, reduce the voriconazole dose by 1 mg/kg or hold 1 dose, and decrease the subsequent dose by 25%. Conclusion: It is recommended that all patients on voriconazole should have their initial dosing program selected on the basis of their hepatic function or other influencing factors (e.g., pathogens, infections, C-reactive protein, albumin, or obesity), and that therapeutic concentrations should be achieved through appropriate dosage adjustments guided by therapeutic drug monitoring. Routine genetic testing for voriconazole application in patients is not considered necessary at this time. However, there has been a great deal of research and partial consensus on individualized dosing of voriconazole, but there are still some critical issues that have not been resolved. [ABSTRACT FROM AUTHOR]

Purpose This article identifies, prioritizes, and summarizes published literature on the medication-use process (MUP) from calendar year 2023 that can impact health-system pharmacy daily practice. The MUP is the foundational system that provides the framework for safe medication utilization within the healthcare environment. The MUP is defined in this article as having the following components: prescribing/transcribing, dispensing, administration, and monitoring. Articles evaluating at least one step of the MUP were assessed for their usefulness toward practice improvement. Summary A PubMed search was conducted in January 2024 for calendar year 2023 using targeted Medical Subject Headings keywords and the tables of contents of selected pharmacy journals were searched, providing a total of 5,314 articles. A thorough review identified 40 potentially practice-enhancing articles: 8 for prescribing/transcribing, 15 for dispensing, 6 for administration, and 11 for monitoring. The trends from the articles are briefly summarized, with a mention of the importance within health-system pharmacy. The articles are listed and summarized in tables for further review and evaluation. Conclusion It is important to routinely review the published literature and to incorporate significant findings into daily practice. This article assists in identifying and summarizing the most impactful literature from 2023. Health-system pharmacists have an active role in improving the MUP in their institutions, and awareness of significant published studies can assist in changing practice at the institutional level. [ABSTRACT FROM AUTHOR]

Objective Method Results Discussion Blood‐based biomarkers and neuroimaging techniques have improved our understanding of the underlying biology of eating disorders (EDs) and have increased our diagnostic portfolio.This editorial accompanies an article collection on novel biological approaches to treat EDs.The collection covers intermittent theta burst stimulation, therapeutic drug monitoring, pharmacological treatments (olanzapine, metreleptin, psychedelics, and anti‐inflammatory medications), microbiome‐based treatments such as pro‐ and prebiotics, as well as individually tailored treatment approaches for EDs.Research of brain areas and bodily systems that are related to memory, emotions and immune function will hopefully expand the biological treatment options for people with EDs. [ABSTRACT FROM AUTHOR]

Objective To investigate the status of drug resistance of Mycobacterium tuberculosis ( M. tuberculosis ) isolated from drug resistance monitoring stations in Changsha from 2021 to 2023, and to provide reference for the control effect of drug -resistant tuberculosis. Methods The positive specimens from designated medical institutions in Changsha were collected and sent to our hospital together with the basic information of patients for further M. tuberculosis drug susceptibility test. Drug susceptibility tests were performed on all samples by proportional method, including 8 drugs, such as RFP, INH, EMB, SM, OFX, PAS, TH, KM, etc, and the qualitative data were analyzed by χ² test. Results Among the 3 037 isolates, 2 534 were fully sensitive and 503 were drug - resistant, and the total drug resistance rate was 16. 56% . Among them, 316 were single drug resistant, and the drug resistance rate was 10. 41%. There were 81 multi - drug resistant strains (2. 67% ) and 106 poly - drug resistant strains (3. 49% ). The drug resistance sequences of any drug were INH, SM and RFP, 9. 02%, 6. 98% and 3. 65%, respectively. The top three of multi - drug resistant patterns were INH + RFP (0. 66% ), INH + RFP + SM (0. 4% ) and INH + RFP + SM + EMB (0. 36% ), respectively. The top three poly - drug resistant patterns were INH + SM (1. 15% ), INH + TH1321 (0. 4% ) and INH + EMB (0. 2% ), respectively. In addition, from year of 2021 to 2023, the resistance of M. tuberculosis to RFP, EMB, and TH1321 drugs in Changsha area showed a decreasing trend year by year (P <0. 05), but the overall resistance rate of patients in Changsha urban area was significantly higher than that in other districts and counties. Conclusion Compared with other provinces and cities, the overall drug resistance rate of tuberculosis patients in Changsha is low, but the drug resistance rate of tuberculosis in Changsha urban area is significantly higher than that in other districts and counties, which should arouse the attention of relevant departments. [ABSTRACT FROM AUTHOR]

The advancement of biomedical technologies has introduced a promising approach for targeted drug delivery—utilizing nano and microscale systems. These compounds provide the potential for precise drug delivery to specific tissues, enhancing diagnostic accuracy and therapeutic efficacy, thereby minimizing off-target effects and improving site-specific accumulation. They enable controlled release of therapeutic agents, reducing the systemic toxicity often associated with conventional drugs. This review particularly highlights the critical role of cell membrane-decorated nanocompounds (CDCs), which represent a significant innovation in this field. Artificial Intelligence (AI) plays a pivotal role in enhancing the precision of CDCs, utilizing advanced algorithms to predict optimal delivery routes and release mechanisms. Moreover, AI-driven analytics are instrumental in the real-time monitoring and adjustment of drug release rates, ensuring maximum efficacy and patient safety. This review delves into the applications of CDCs, exploring their characterization, drug delivery potential, and future prospects, with a specific focus on how cell membrane coatings can revolutionize the landscape of drug delivery. Furthermore, the integration of AI in these processes is emphasized, particularly in how it can significantly impact future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: The practice of therapeutic drug monitoring (TDM) is widely used for maximizing the clinical efficacy of antimicrobials. However, a systematic bibliometric analysis providing an overview of this field is lacking at present. The aim of the current study was to identify hotspots and trends in antimicrobial TDM, highlight collaborations and influences among countries, institutions, and journals, and assess the knowledge base for further development of clinical research. Research Design and Methods: Articles and reviews related to TDM of antimicrobials from the Web of Science Core Collection were collected. CiteSpace and VOSviewer, two visualization tools, were utilized to graphically assess the key elements within this domain, including mapping of countries and regions, institutions, keywords, and references associated with the field of antimicrobial TDM. Through this approach, we were able to successfully provide a comprehensive visual overview of the research landscape, highlighting the significant players and thematic trends in the literature. Results: From 2000 to 2023, a total of 17,236 authors from 4,112 institutions in 112 countries/regions published 3,710 papers in 819 academic journals. The United States had the highest number of publications, with University of Queensland identified as the most active institution. The journal with the greatest number of publications was Therapeutic Drug Monitoring, whereas Antimicrobial Agents and Chemotherapy was the most co-cited journal. Current research focuses on pharmacokinetics, pharmacodynamics, vancomycin, posaconazole, invasive fungal infection and critically ill patients. Promising hotspots for future research include vancomycin, voriconazole, meropenem, isavuconazole, posaconazole, and teicoplanin. Moreover, vancomycin and critically ill patients remain a hot topic of future research. Conclusion: Using bibliometric and visualization methods, the research hotspots of antimicrobial drugs in TDM were analyzed. The continued increase in the number of annual publications demonstrates the vital significance of TDM for antimicrobials. Data from this study provide a valuable reference for future research trends in TDM of antimicrobial agents. [ABSTRACT FROM AUTHOR]

Introduction: Pneumonia remains a significant global health challenge due to its high prevalence and mortality rate, and challenging treatment. This review explores the best strategies to optimize the antibiotic therapy for pneumonia in critically ill patients, focusing on pharmacokinetics, pharmacodynamics, and therapeutic data. Areas covered: A review of scientific publications on severe pneumonia highlights the challenges of optimizing antibiotic use to improve lung diffusion, bacterial killing, and achieving PK/PD targets, emphasizing the need to understand microbiological epidemiology and MIC breakpoints. Key strategies like nebulization, therapeutic drug monitoring, and emerging technologies such as ELF TDM and nanomaterial-based drug delivery systems are essential for optimizing PK/PD outcomes and addressing antimicrobial resistance. Expert opinion: Improving our understanding of pulmonary pharmacokinetics and optimizing their tissue diffusion are instrumental for achieving precision antibiotic therapy for severe pneumonia. By addressing current limitations and embracing interdisciplinary collaboration, we can pave the way for more efficient personalized approaches in infectious disease management. [ABSTRACT FROM AUTHOR]

Maintaining adequate levels of antiretroviral (ARV) medications is crucial for the efficacy of HIV treatment and prevention regimens. Monitoring ARV levels can predict or prevent adverse health outcomes like treatment failure or drug resistance. However, conventional ARV measurement using liquid chromatography-tandem mass spectrometry (LC–MS/MS) is slow, expensive, and centralized delaying clinical and behavioral interventions. We previously developed a rapid enzymatic assay for measuring nucleotide reverse transcriptase inhibitors (NRTIs) — the backbone of HIV treatment and prevention regimens — based on the drugs' termination of DNA synthesis by HIV reverse transcriptase (RT) enzyme. Here, we expand our work to include non-nucleoside reverse transcriptase inhibitors (NNRTIs) — an ARV class used in established and emerging HIV treatment and prevention regimens. We demonstrate that the REverse Transcriptase ACTivity (REACT) assay can detect NNRTIs including medications used in oral and long-acting/extended-release HIV treatment and prevention. We demonstrate that REACT can measure NNRTIs spiked in either buffer or diluted plasma and that fluorescence can be measured on both a traditional plate reader and an inexpensive portable reader that can be deployed in point-of-care (POC) settings. REACT measured clinically relevant concentrations of five NNRTIs spiked in aqueous buffer. REACT measurements showed excellent agreement between the plate reader and the portable reader, with a high correlation in both aqueous buffer (Pearson's r = 0.9807, P < 0.0001) and diluted plasma (Pearson's r = 0.9681, P < 0.0001). REACT has the potential to provide rapid measurement of NNRTIs in POC settings and may help to improve HIV treatment and prevention outcomes. [ABSTRACT FROM AUTHOR]

In the treatment of diseases such as acute childhood leukaemia (ALL) and inflammatory bowel disease (IBD), the thiopurines azathioprine, 6-mercaptopurine, and 6-thioguanine are used. Thiopurines are antimetabolites and immunomodulators used to maintain remission in patients. They are all prodrugs and must be converted into the competing antimetabolites thioguanosine triphosphate and deoxythioguanosine triphosphate for final incorporation into RNA or DNA. The current therapeutic drug monitoring (TDM) method measures the sum of the formed metabolites in the sample, after acidic hydrolysis at high temperature. In this work, the goal is to measure these drugs closer to their pharmacological endpoints, once incorporated into DNA. After extracting DNA from whole blood, followed by DNA hydrolysis, 2′-deoxythioguanosine (dTG) and the complementary natural nucleobase 2′-deoxycytidine (dC) were measured. Chromatographic separation on a HSS T3 column followed by mass spectrometric detection was performed in multi-reaction monitoring (MRM) mode on a Xevo TQ-XS with ESI in positive mode, within 5 min. The concentration range for dTG was 0.04–5 nmol/L, and for dC, 0.1–12.5 µmol/L. The lower limit of detection was determined to a concentration of 0.003 nmol/L for dTG and 0.019 µmol/L for dC. The intra- and inter-assay imprecision for the quality controls ranged between 3.0 and 5.1% and between 8.4 and 10.9%, respectively. Sample stability for up to 4 years is shown. In summary, a sensitive method to quantify the thiopurines incorporated into DNA as dTG has been developed and will be used in further clinical studies for a better understanding of the mode of action of the thiopurines and the use of this method in TDM. [ABSTRACT FROM AUTHOR]

Background: This study provides an overview of the clinical applications of drugs and their metabolites analysis in biological fluids and identifies commonly used analytical techniques for bioanalysis. Methods: Original open-access articles published between 31 October 2005 and 31 October 2020 in Google Scholar, MEDLINE, PubMed, and Embase were reviewed, and pertinent findings of the individual studies were pooled and presented using tables. This review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Results: Fifteen studies met the eligibility criteria and were included in the review. These studies show that qualitative identification and quantitative determination of drugs and their metabolites in biological fluids are important for therapeutic drug monitoring (TDM), pharmacokinetic and pharmacodynamic studies, drug abuse control, and forensic and toxicological analyses. Spectroscopic, electrochemical, and hyphenated and nonhyphenated chromatographic techniques are used to analyse drugs and their metabolites in biological fluids. However, hyphenated techniques are the preferred analytical methods because of their sensitivity, selectivity, accuracy, reproducibility, efficiency, and rapid analysis. Conclusion/Recommendations: Bioanalysis is important for pharmacokinetic and pharmacodynamic studies, therapeutic drug monitoring, forensic and toxicological analyses, and drug abuse control using different bioanalytical techniques. However, hyphenated techniques are the most commonly used bioanalytical techniques. Bioanalysis of drugs and their metabolites needs to be improved to provide good medical and pharmaceutical care to patients, to confirm forensic and toxicological cases, and to control drug abuse. [ABSTRACT FROM AUTHOR]

Background: High-dose methotrexate (HD-MTX) is commonly employed in the treatment of malignant tumors in children and young adults due to its distinctive therapeutic efficacy. Nonetheless, the systemic exposure to MTX often results in liver injury (drug induced liver injury, DILI), thereby imposing limitations on the sustained administration of HD-MTX. Additionally, individual variations including genetic underpinnings attributable to disparities in therapeutic effects and clinical toxicity remain to be elucidated. Methods: A total of 374 patients receiving initial HD-MTX treatment were selected for this study, which aimed to establish a predictive model using binary logistic regression and a visual nomogram for DILI risk assessment. Demographic and clinical characteristics were collected at baseline and post-HD-MTX to explore their correlations with the occurrence of DILI. Additionally, genotyping of 25 single nucleotide polymorphisms from drug transporters and enzymes in the folic acid cycle was performed. Result: G allele mutation in ABCB1 rs1128503, *1b/*1b and *1b/*15 haplotypic mutation in SLCO1B1 , female gender, and MTX dosage were identified as independent factors for moderate/severe DILI. Patients with GA or AA genotype in ABCB1 rs1128503 showed significant higher 24h MTX concentration than GG, and those with *1b/*1b haplotype group in SLCO1B1 exhibited lower dose adjusted concentration (C/D) than *1a/*1a group. Besides, patient administrated with HD-MTX were more prevalent to have higher C/D levels when using intravenous plus triple intrathecal injection route than those who were using intravenous injection alone. The composite predictive model (ROC curve: AUC = 0.805), comprising above four factors and 24h MTX concentration, exhibited high accuracy. Conclusion: Female gender, recessive mutation in ABCB1 rs1128503, and a range of MTX concentration may be risk factors for increased susceptibility to DILI. Conversely, the *1b/*1b and *1b/*15 mutations in SLCO1B1 may have a protective effect against DILI. The proposed predictive model facilitates early individual risk assessment, enabling the implementation of proactive prevention strategies. [ABSTRACT FROM AUTHOR]

Three‐dimensional (3D) spheroid models offer a more physiologically relevant and complex environment compared to traditional two‐dimensional cultures, making them a promising tool for studying tumor biology and drug response. However, these models often face challenges in real‐time monitoring of drug diffusion, penetration, and target engagement, limiting their predictive power for in vivo and clinical outcomes. This study introduces a novel approach for real‐time tracking of drug permeability using small molecule drugs with GFP/RFP‐disrupting properties that correlate with their efficacy. We developed a reproducible 3D spheroid model with various cancer cell lines expressing GFP/RFP for efficient drug screening. Through screening over 20 FDA‐approved enzyme inhibitors, we identified three covalent kinase inhibitors—osimertinib, afatinib, and neratinib—that irreversibly disrupt GFP and RFP fluorescence. Our results reveal distinct drug diffusion and penetration profiles within GFP/RFP‐expressing spheroids, varying with drug concentration and formulation, and correlating with clinical volume of distribution (Vd) values. Additionally, we demonstrate that our approach is useful for evaluating different drug formulations as well as screening penetration enhancers for solid tumors. These findings offer a valuable 3D model for studying kinetics of drug permeability and efficacy in tumor‐like environments, with potential implications for drug delivery research and formulation development. [ABSTRACT FROM AUTHOR]

Pharmacovigilance plays a crucial role in ensuring the safety of pharmaceutical products. It involves the systematic monitoring of adverse events and the detection of potential safety concerns related to drugs. Manual literature screening for pharmacovigilance related articles is a labor-intensive and time-consuming task, requiring streamlined solutions to cope with the continuous growth of literature. The primary objective of this study is to assess the performance of Large Language Models (LLMs) in automating literature screening for pharmacovigilance, aiming to enhance the process by identifying relevant articles more effectively. This study represents a novel application of LLMs including OpenAI's GPT-3.5, GPT-4, and Anthropic's Claude2, in the field of pharmacovigilance, evaluating their ability to categorize medical publications as relevant or irrelevant for safety signal reviews. Our analysis encompassed N-shot learning, chain-of-thought reasoning, and evaluating metrics, with a focus on factors impacting accuracy. The findings highlight the promising potential of LLMs in literature screening, achieving a reproducibility of 93%, sensitivity of 97%, and specificity of 67% showcasing notable strengths in terms of reproducibility and sensitivity, although with moderate specificity. Notably, performance improved when models were provided examples consisting of abstracts, labels, and corresponding reasoning explanations. Moreover, our exploration identified several potential contributing factors influencing prediction outcomes. These factors encompassed the choice of key words and prompts, the balance of the examples, and variations in reasoning explanations. By configuring advanced LLMs for efficient screening of extensive literature databases, this study underscores the transformative potential of these models in drug safety monitoring. Furthermore, these insights gained from this study can inform the development of automated systems for pharmacovigilance, contributing to the ongoing efforts to ensure the safety and efficacy of pharmacovigilance products. [ABSTRACT FROM AUTHOR]

Background and Aims: The powerful antihyperlipidemic drug rosuvastatin blocks 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is essential for cholesterol formation. Statins are a more recent class of antihyperlipidemic medications. Accurate quantification methods are crucial because of low rosuvastatin levels in tablets. The following the International Conference on Harmonisation (ICH) guidelines, a sensitive and high-performance liquid chromatographic approach was established in this study for the accurate determination of rosuvastatin in tablet formulations using spectrofluorimetric detection. Methods: The procedure requires one hour at room temperature and dark interaction between the acid group of rosuvastatin and the reagent 9-anthryldiazomethane. A C18 column (250 x 4.6 mm, 4 µm) was used for the gradient elution of an acetonitrile-water solution at a flow rate of 1.0 mL/min to achieve chromatographic separation. The internal reference was lovastatin. The excitation and emission wavelengths used for the detection were 366 and 410 nm, respectively. Results: Calibration curves for standard solutions were established by plotting the ratio of concentration to peak area over the range 0.01–20.0 ng/mL. The limits of quantification (LOQ) and detection (LOD) were 0.0068 and 0.0023 ng/mL, respectively. The relative standard deviation values for interday and intraday measurements of the standard solutions ranged from 0.24% to 3.76%. The mean recoveries for 0.240. in the tablet formulation were calculated as 98.0-99.9%. Conclusion: The developed method was used to determine the amount of rosuvastatin in tablets, and the results were compared with a 95% confidence level to those obtained using a literature method. The suggested approach works well for sensitive routine analysis and monitoring of drugs at low concentrations to investigate their bioavailability and bioequivalence. [ABSTRACT FROM AUTHOR]

Objectives Therapeutic drug monitoring (TDM) is recommended for posaconazole to achieve target concentrations of ≥0.7 mg/L and ≥1.0 mg/L for prophylaxis and treatment of invasive fungal infection (IFI), respectively. However, target attainment is challenging with the oral suspension, particularly in children. Here, we describe our experience using crushed delayed-release tablet (DRT) in a paediatric cohort, with a focus on TDM. Methods We undertook a retrospective audit of crushed posaconazole DRT administration via enteral feeding tubes (EFTs) for patients aged ≤18 years over 18 months at The Royal Children's Hospital Melbourne who had at least one trough concentration measured at steady state. Details of patient demographics, posaconazole dosing, monitoring and adverse effects were recorded. Results Twelve patients with a median age of 9 years (range 2 to 14) received posaconazole DRT via EFT for prophylaxis (n  = 8) or treatment (n  = 4). All children achieved target concentration, with a median dose of 7 mg/kg/day (range 5 to 11) for prophylaxis and 13 mg/kg/day (range 9 to 20) for treatment. The median time to reach therapeutic levels was 7 days (range 5 to 14) for prophylaxis and 20 days (range 15 to 35) for treatment. One child had blockage of their EFT, which was attributed to posaconazole. No other adverse effects were observed. Conclusions Crushed posaconazole DRT administered via EFT may be used as a method of attaining therapeutic posaconazole concentrations in children for antifungal prophylaxis and treatment. [ABSTRACT FROM AUTHOR]

Background Continuous renal replacement therapy (CRRT) complicates antibiotic dosing in critically ill patients due to altered pharmacokinetics. The optimal dosing of piperacillin remains unclear. Therapeutic drug monitoring (TDM) can personalize piperacillin therapy and improve outcomes. Objectives This review investigates the effects of TDM-guided piperacillin dosing on pharmacokinetic target attainment and clinical outcomes in CRRT patients, analyses correlations with clinical outcomes, provides optimal dosing strategies for piperacillin and identifies future research areas. Methods A systematic search of PubMed, Scopus and Web of Science was conducted until December 2023, identifying studies on piperacillin pharmacokinetics and clinical outcomes in adult CRRT patients. Data on study characteristics, piperacillin exposures, TDM use, target attainment rates, mortality and length of stay were extracted. The risk of bias was assessed using the Newcastle–Ottawa Scale. Results Eleven observational studies were included. High pharmacokinetic variability was evident, with piperacillin target non-attainment in up to 74% of cases without TDM. Two studies with routine TDM showed increased target attainment rates of 80%–100%. Mortality ranged from 17% to 56%, with supratherapeutic concentrations (≥100 mg/L) associated with higher mortality. The impact of optimized piperacillin exposures on outcomes was inconclusive. Most studies demonstrated a low risk of bias. Conclusions TDM-guided piperacillin dosing in CRRT patients improved target attainment rates (≥80%). Mortality rates ranged from 17% to 56%, with inconsistent correlations between drug exposures and survival. Supratherapeutic concentrations were linked to higher mortality. Standardized TDM protocols are needed. Future research should establish clear exposure–response relationships and the impact of TDM on clinical outcomes. [ABSTRACT FROM AUTHOR]

Proteins as crucial components of cells are responsible for the majority of cellular processes. Sensitive and efficient protein detection enables a more accurate and comprehensive investigation of cellular phenotypes and life activities. Here, a protein sequencing method with high multiplexing, high throughput, high cell utilization, and integration based on digital microfluidics (DMF‐Protein‐seq) is proposed, which transforms protein information into DNA sequencing readout via DNA‐tagged antibodies and labels single cells with unique cell barcodes. In a 184‐electrode DMF‐Protein‐seq system, ≈1800 cells are simultaneously detected per experimental run. The digital microfluidics device harnessing low‐adsorbed hydrophobic surface and contaminants‐isolated reaction space supports high cell utilization (>90%) and high mapping reads (>90%) with the input cells ranging from 140 to 2000. This system leverages split&pool strategy on the DMF chip for the first time to overcome DMF platform restriction in cell analysis throughput and replace the traditionally tedious bench‐top combinatorial barcoding. With the benefits of high efficiency and sensitivity in protein analysis, the system offers great potential for cell classification and drug monitoring based on protein expression at the single‐cell level. [ABSTRACT FROM AUTHOR]

Background Aims Methods Results Conclusions Antimicrobial stewardship (AMS) guidelines now recommend antifungal stewardship (AFS) interventions to improve the management of invasive fungal diseases (IFDs). AFS programmes have not been reported in Australia.To determine the monitoring of antifungal use, AFS strategies and targets, and barriers to AFS implementation in Australian hospitals.An electronic quantitative cross‐sectional survey was developed and distributed to public and private hospitals in Australia in February 2018. Descriptive statistics were used to summarise the findings.Eighty‐three Australian hospitals completed the survey with an overall response rate of 58% (83/143). Most hospitals monitored antifungal use (62/83, 75%). Frequently used AFS metrics included costs (48/60, 80%) and yearly point prevalence surveys (45/60, 75%). Core AFS strategies were commonly in place, including preauthorisation requirements (71/80, 89%) and expert antifungal post‐prescription review and feedback (PPRF) (63/80, 79%). Both these strategies were more strictly applied to high‐cost, intravenous agents. Formal education (44/79, 56%) and hospital‐endorsed guidelines (35/79, 44%) were modestly used. Fungal diagnostics and antifungal therapeutic drug monitoring (TDM) were utilised, largely off site. IFD surveillance was infrequently performed (9/77, 12%). Barriers to AFS identified included lack of staff time, prioritisation of AFS, and access to rapid diagnostics and TDM.AFS strategies utilised in Australian hospitals have focused on high‐cost, intravenous agents. Although expert oversight of antifungals is evident, many sites omit potentially important targets for AFS, including fluconazole and oral posaconazole. Identifying these gaps and barriers to AFS will guide the development of an AFS model for hospitals. [ABSTRACT FROM AUTHOR]

The article presents letter to the editor focuses on evaluating the heparin-calibrated chromogenic anti-Xa assay for detecting threshold levels of direct oral anticoagulants (DOACs) in urgent settings, such as acute ischemic stroke. Topics include the need for accurate assessment of DOAC levels for thrombolytic therapy, the comparison of heparin-calibrated anti-Xa assays with DOAC-specific assays, and the study's findings on the sensitivity and limitations of the heparin-calibrated assay.

The article presents letter to the editor focuses on the validation of a modified Nijmegen method for detecting cross-reactivity of human factor VIII antibodies to recombinant porcine factor VIII in patients with acquired hemophilia A and hemophilia A with inhibitors. Topics include laboratory testing of cross-reactivity using imidazole buffer and factor VIII-deficient plasma, and the clinical implications of antibody cross-reactivity on recombinant porcine factor VIII treatment.

Simple Summary: The analysis of the interaction between incident light and matter can reveal certain properties about the matter itself. This phenomenon can be utilised in the form of Raman spectroscopy. The application of Raman spectroscopy to biological matrices may enable both quantitative and qualitative analysis of the sample. There are many potential applications in medicine, particularly in oncology. Individualisation of care may be achieved by precisely measuring drug exposure in therapeutic drug monitoring, as well as precisely assessing treatment response by measuring changes in tumour DNA levels in the blood. The existing methods to measure these parameters are expensive, specialized and time-consuming. Raman spectroscopy may provide a more accessible and highly accurate alternative. Raman spectroscopy is a technique which involves quantitative and qualitative molecular analysis based on the interaction between incident light and isolation of scattered wavelengths in generating a molecular fingerprint. It has a broad array of potential scientific applications, encompassing areas as diverse as food science and forensics. However, it may also be highly useful in clinical oncology. A recent focus of research in oncology has been in achieving the individualisation of care. Two important strategies to achieve a so-called "precision oncology" approach may include the detection of circulating tumour DNA (ctDNA) in more objectively evaluating treatment response and guiding de-escalation and intensification approaches in systemic therapy and therapeutic drug monitoring (TDM). Therapeutic drug monitoring involves the quantitation of plasma drug levels in order to tailor medication dosing in optimizing outcomes. The existing approaches to characterize small molecules, such as fluorescence-based and chromatographic strategies, may be limited by high costs, long turnaround times, and bulky equipment. Surface-enhanced Raman spectroscopy (SERS) may be deployed by utilizing a handheld device, with the potential for point of care, rapid turnaround, low-cost assessment of clinically relevant parameters, and prompt implementation of attendant changes in treatment. Although there is a growing body of data supporting the implementation of TDM and evaluation of ctDNA in achieving precision medicine, the uptake of such approaches remains relatively limited outside of clinical trials. As stated, the nature of existing analytical methodologies may prove to be a significant barrier to the routine clinic-based implementation of such approaches. Therefore, we provide the existing evidence for SERS in alleviating these barriers. We also provide insights into how SERS could contribute to clinical oncology. [ABSTRACT FROM AUTHOR]

The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29‐year‐old Japanese primipara with treatment‐resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N‐desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages. [ABSTRACT FROM AUTHOR]

Background: High-dose methotrexate (HDMTX) chemotherapy is associated with a significant risk of acute kidney injury (AKI). Acetazolamide is thought to increase methotrexate solubility via urinary alkalinisation, potentially reducing the risk of crystalline nephropathy. A tertiary hospital has included acetazolamide in its HDMTX protocols, although data on the risks and benefits are limited. This study evaluated the role of acetazolamide in managing patients receiving HDMTX and identified risk factors for AKI. Methods: The retrospective cohort pilot study included consecutive hospital patients who received HDMTX (≥500 mg/m2). Data collected from digital medical records included demographics, comorbidities, methotrexate dosages and serum concentrations, and pathology results. The development of AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Relationships between variables and AKI were initially assessed using Mann–Whitney U-tests and chi-square tests, and significant variables were further analysed using logistic regression to identify independent predictors of AKI. Results: Among 66 HDMTX treatment cycles in 31 patients, AKI occurred in 0/7 cycles with acetazolamide versus 14/59 cycles without (p = 0.33). Increasing age, the presence of hypertension, and concurrent use of beta-lactam antibiotics were associated with the development of AKI. Age was identified as the strongest independent risk factor for AKI (odds ratio 1.12, p = 0.034). Conclusions: Optimising management protocols, especially for older patients, is essential to reduce AKI risk during HDMTX therapy. While acetazolamide did not appear to reduce the risk of AKI, this pilot study was limited by a small sample size. Large randomised controlled trials are needed to assess efficacy and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Invasive aspergillosis (IA) is an opportunistic infection that affects immunocompromised patients. While voriconazole is commonly used for IA treatment, it presents the risk of drug interactions, particularly in patients on polytherapy. Isavuconazole may serve as a safer alternative with fewer interactions. However, the use of isavuconazole is typically limited to the parenteral route for patients without access to the enteral route, due to recommendations against tablet handling for enteral administration. The objective of this study was to evaluate the suitability of isavuconazole administration via an enteral tube, by therapeutic drug monitoring of isavuconazole plasma concentrations. Methods: This case study examines a patient with diffuse large B-cell lymphoma who was diagnosed with IA and treated with isavuconazole via an enteral tube. Therapeutic pharmacokinetic monitoring of isavuconazole plasma concentrations was performed to assess the feasibility and safety of enteral administration. Results: The results show that isavuconazole concentrations were maintained within the therapeutic range when administered via an enteral tube. No significant deviations in plasma concentration were noted during the monitoring period. Conclusions: Administering isavuconazole through an enteral tube is a safe and viable alternative for patients that are unable to receive the drug via the oral route. Therapeutic monitoring of plasma concentrations is recommended to ensure proper dosing and efficacy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of pharmaceutical intervention on rational application of proton pump inhibitors (PPI) in preventing stress related mucosal disease (SRMD) during perioperative period in this hospital. METHODS: Case data of 295 patients with surgery received PPI in preventing SRMD during perioperative period in 2021 (before intervention) and 2022 (after intervention) were extracted from hospital information system (HIS), including 144 cases before intervention and 151 cases after intervention. Indicators including the application rate with indications, effective medication frequency, rational medication evaluation and safety evaluation of patients with preventive application of PPI during perioperative period were statistically analyzed. RESULTS: Compared with before intervention, the application rate with indications increased from 72. 22% (104/144) to 83. 44% (126/151), the proportion of DDDs in effective varieties increased from 64. 31% (953. 33/1 482. 33) to 92. 31% (1 541. 67/1 670. 17), the rational rate of variety selection increased from 63. 89% (92/144) to 93. 38% (141/151), the rational rate of administration frequency increased from 48. 61% (70/144) and 77. 48% (117/151), the rational rate of administration route increased from 68. 06% (98/144) to 84. 11% (127/151), the rational rate of administration course increased from 72. 22% (104/144) to 83. 44% (126/151) in patients with preventive application of PPI during perioperative period in the hospital, with statistically significant differences (P< 0. 05). The rational rate of single dose and rational rate of solvent use were respectively 100. 00% and 98. 01% (148/151) after intervention, both higher than those of before intervention [99. 31% (143/144) and 95. 14% (137/144)], while the differences were not statistically significant (P>0. 05). The differences in the comparisons of incidences of SRMD, incidences of adverse drug reactions and length of hospital stay among patients before and after intervention were not statistically significant (P > 0. 05). CONCLUSIONS: Pharmaceutical intervention can effectively increase the rationality of preventing application of PPI during perioperative period in the hospital, which is conducive to reducing medication risk and relieving financial burden of patients, and is worthy of promotion in the management and control of other key monitoring drugs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the characteristics and rules of adverse drug reactions (ADR) of drugs in national centralized volume-based procurement in Dongguan, so as to provide reference for clinical rational drug use. And to identify the high-risk drug categories with the highest number of severe ADR cases, so as to initially screen out the primary suspected drugs for the signal mining. METHODS: Through the spontaneous reporting system of the National Adverse Drug Reaction Monitoring Platform, 5 032 reports of ADR of drugs in national centralized volume-based procurement in Dongguan from 2020 to 2023 were collected for statistics, analysis and evaluation. RESULTS: Among the 5 032 reports of ADR of drugs in national centralized volume-based procurement, there were more females than males, with a gender ratio (males: females) of 0. 93: 1. The proportion of patients aged from >15 to 45 years was the highest (41. 34%, 2 080 cases). Totally 45. 81% (2 305 cases) of patients had a history of ADR, and 58. 03% (2 920 cases) had unknown family history of ADR. The main route of administration was oral administration (2 982 cases, 59. 26%), followed by injection (1 888 cases, 37. 52%). ADR occurred mainly within 1 h (1 475 cases, 29. 31%), >1 to 3 d (1 077 cases, 21. 40%) and >12 to 24 h (921 cases, 18. 30%) after administration. The types of drugs involved in ADR were mainly chemical drugs (4 973 cases, 98. 83%). The top 2 drug categories ranked by the number of ADR reports were anti-infective drugs (2 438 cases, 48. 45%) and cardiovascular system drugs (599 cases, 11. 90%). The top 2 drug categories ranked by the number of severe ADR reports were anti-infective drugs (719 cases, 14. 29%) and tumor drugs (83 cases, 1. 65%). A total of 5 838 cases of organs and (or) systems were involved, mainly skin and subcutaneous tissues (2 380 cases, 40. 77%). After treatment, 97. 71% of the patients (4 917 cases) were improved or recovered. CONCLUSIONS: It is necessary to carry out ADR monitoring of drugs in national centralized volume-based procurement, strengthen the analysis and evaluation of surveillance data, and focus on new and severe ADR, as well as ADR of anti-infective drugs, cardiovascular system drugs, and antitumor drugs. [ABSTRACT FROM AUTHOR]

Aims: Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6‐thioguanine nucleotides (6‐TGN), 6‐methylmercaptopurine ribonucleotides (6‐MMPR) and the 6‐MMPR/6‐TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes. Methods: A post‐hoc analysis was conducted of a multicentre, prospective, observational study on thiopurine‐induced hepatotoxicity. IBD patients who initiated thiopurine therapy were included and thiopurine metabolite concentrations were assessed after 7 days (±1) (T1). Patients were monitored for 12 weeks to document the occurrence of ADRs, early treatment discontinuation and effectiveness. Results: In total, 181 patients were evaluated. At T1, 6‐MMPR concentrations and 6‐TGN/6‐MMPR ratios were independently related to treatment discontinuation within 12 weeks after correction for sex, age and body mass index (BMI) (P =.034 and.002, respectively). The largest effects were observed for 6‐MMPR ≥3000 pmol/8 × 108 RBC and 6‐TGN/6‐MMPR ratio ≥17. Furthermore, 6‐MMPR concentrations and 6‐TGN/6‐MMPR ratios at T1 were independently related to skewed metabolism at steady state (Week 8, 6‐MMPR/‐6TGN ratio ≥11 and ≥20) (both P <.001). The occurrence of ADRs and effectiveness were not independently related to T1 thiopurine metabolite concentrations. Conclusions: Thiopurine metabolite concentrations at T1 were related to early treatment discontinuation and skewed metabolism at steady state, but not to effectiveness, helping to identify patients with a high risk of thiopurine treatment failure. [ABSTRACT FROM AUTHOR]

Objective: Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of intravenous (iv) insulin treatment. The aim of this study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Methods: Clinical data from extremely premature infants (<28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia in the neonatal intensive care unit were included. Blood glucose levels during CSII, as well as the nutritional intake and insulin intake were recorded. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Results: Normoglycemia rates were best in the iv insulin-cohort (n=22, 50.3%) compared to the CSII group (n=15, 15.6%). Hypoglycemia was very rare in both groups (0.4% vs. 0.0%). CSII therapy appears to require higher insulin doses compared to continuous iv therapy to achieve a similar effect. Subcutaneous Insulin therapy in extremely preterm infants is feasible, at least for prevention of hypoglycemia. However, dose control needs to be improved. Conclusion: The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII in this population. [ABSTRACT FROM AUTHOR]

Mass-spectrometry-based assays nowadays play an essential role in biomedical research and clinical applications. There are different types of commercial mass spectrometers on the market today, and triple quadrupole (QqQ) is one of the time-honored systems. Here, we overview the main areas of QqQ applications in biomedicine and assess the current level, evolution, and trends in the use of QqQ in these areas. Relevant data were extracted from the Scopus database using the specified terms and Boolean operators defined for each field of the QqQ application. We also discuss the recent advances in QqQ and QqQ-based analytical platforms, which promote the clinical application of these systems, and explain the indicated substantial increase in triple quadrupole use in biomedicine. The number of biomedical studies utilizing QqQ increased 2–3 times this decade. Triple quadrupole is most intensively used in the field of endocrine research and testing. On the contrary, the relative rate of immunoassay utilization—a major competitor of chromatography–mass spectrometry—decreased in this area as well as its use within Therapeutic drug monitoring (TDM) and forensic toxicology. Nowadays, the applications of high-resolution accurate mass (HRAM) mass spectrometers in the investigated areas represent only a small fraction of the total amount of research using mass spectrometry; however, their application substantially increased during the last decade in the untargeted search for new biomarkers. [ABSTRACT FROM AUTHOR]

The document "Nano-Functional Materials for Sensor Applications" published in the journal Molecules highlights the advancements in sensor technology driven by nanotechnology and materials science. It emphasizes the importance of nano-functional materials in designing high-performance sensors for healthcare monitoring, environmental protection, and security applications. The document discusses the molecular-level interactions and chemical properties of these materials, showcasing their applications in various fields such as healthcare, environmental monitoring, and food safety. The research articles and reviews included in the Special Issue demonstrate innovative approaches to sensor development, combining advanced materials science with practical applications in real-world scenarios. [Extracted from the article]