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Mercury contamination has been aggravated by emerging environmental issues, such as climate change. Top predators present concerning Hg concentrations once this metal bioaccumulates and biomagnifies. This study evaluated total mercury (THg) concentrations in tissues of 43 franciscanas (Pontoporia blainvillei) from two populations: the Franciscana Management Area (FMA) IIb and FMA IIIa. Animals from FMA IIIa showed mean concentration 5-times and 2.5-times higher in the liver and kidney (4.73 ± 6.84 and 0.52 ± 0.51 µg.g-1, w.w., respectively) than individuals from FMA IIb (0.89 ± 1.04 and 0.22 ± 0.15 µg.g-1, w.w., respectively). This might be due to: (I) individuals sampled from FMA IIIa being larger and older, and/or (II) the area near FMA IIIa presents environmental features leading to higher THg availability. Coastal contamination can affect franciscanas’ health and population maintenance at different levels depending on their life history and, therefore, it should be considered to guide specific conservation actions. [ABSTRACT FROM AUTHOR]

Little is known about microplastics (MPs) in adult frogs. We investigated MPs in adult Common River Frogs (Amietia delalandii) from Potchefstroom, South Africa. Five kinds of samples were analysed: natural water, water used to rinse the skin, skin, intestine, and the remainder of the body (corpus). Tissues were digested. Microplastics occurred in all frogs and sample types (1128 MPs counted). Fibres were the most prevalent MP. Fibre lengths were between 28 and 4300 μm, either polyester or polyvinyl alcohol. MPs in skin were likely derived from the ambient, and MPs in the corpus from translocation via the skin. Fibres in tissues were significantly shorter in larger frogs, a phenomenon we provisionally assign to in situ biodegradation. Microplastics in frogs can potentially be transferred through the food web to higher trophic levels. This study provides the first evidence of MPs in adult frog tissues and avenues for further investigations. [ABSTRACT FROM AUTHOR]

Many epidemiological studies have emphasised the relation between carotenoid dietary intake and their circulating concentrations and beneficial health effects, such as lower risk of cardiometabolic diseases and cancer. However, there is dispute as to whether the attributed health benefits are due to native carotenoids or whether they are instead induced by their metabolites. Several categories of metabolites have been reported, most notably involving (a) modifications at the cyclohexenyl ring or the polyene chain, such as epoxides and geometric isomers, (b) excentric cleavage metabolites with alcohol-, aldehyde- or carboxylic acid-functional groups or (c) centric cleaved metabolites with additional hydroxyl, aldehyde or carboxyl functionalities, not counting their potential phase-II glucuronidated / sulphated derivatives. Of special interest are the apo-carotenoids, which originate in the intestine and other tissues from carotenoid cleavage by β-carotene oxygenases 1/2 in a symmetrical / non-symmetrical fashion. These are more water soluble and more electrophilic and, therefore, putative candidates for interactions with transcription factors such as NF-kB and Nrf2, as well as ligands for RAR–RXR nuclear receptor interactions. In this review, we discuss in vivo detected apo-carotenoids, their reported tissue concentrations, and potential associated health effects, focusing exclusively on the human situation and based on quantified / semi-quantified carotenoid metabolites proven to be present in humans. [ABSTRACT FROM AUTHOR]

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Macrolide antibiotics are important drugs to combat infections. The pharmacokinetics (PK) of these drugs are essential for the determination of their optimal dose regimens, which affect antimicrobial pharmacodynamics and treatment success. For most drugs, the measurement of their concentrations in plasma/serum is the surrogate for drug concentrations in target tissues for therapy. However, for macrolides, simple reliance on total or free drug concentrations in serum/plasma might be misleading. The macrolide antibiotic concentrations of serum/plasma, interstitial fluid (ISF), and target tissue itself usually yield very different PK results. In fact, the PK of a macrolide antibiotic based on serum/plasma concentrations alone is not an ideal predictor for the in vivo efficacy against respiratory pathogens. Instead, the PK based on drug concentrations at the site of infection or ISF provide much more clinically relevant information than serum/plasma concentrations. This review aims to summarize and compare/discuss the use of drug concentrations of serum/plasma, airway ISF, and tissues for computing the PK of macrolides. A better understanding of the PK of macrolide antibiotics based on airway ISF concentrations will help optimize the antibacterial dose regimen as well as minimizing toxicity and the emergence of drug resistance in clinical practice. [ABSTRACT FROM AUTHOR]

It is well known that coenzyme Q10 (CoQ10) has important antioxidant properties. Because one of the main mechanisms involved in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases is oxidative stress, analysis of the concentrations of CoQ10 in different tissues of AD patients and with other dementia syndromes and the possible therapeutic role of CoQ10 in AD have been addressed in several studies. We performed a systematic review and a meta-analysis of these studies measuring tissue CoQ10 levels in patients with dementia and controls which showed that, compared with controls, AD patients had similar serum/plasma CoQ10 levels. We also revised the possible therapeutic effects of CoQ10 in experimental models of AD and other dementias (which showed important neuroprotective effects of coenzyme Q10) and in humans with AD, other dementias, and mild cognitive impairment (with inconclusive results). The potential role of CoQ10 treatment in AD and in improving memory in aged rodents shown in experimental models deserves future studies in patients with AD, other causes of dementia, and mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) has an important role as an antioxidant. Being that oxidative stress is one of the mechanisms involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases, several studies addressed the concentrations of CoQ10 in the different tissues of patients with PD and other parkinsonian syndromes (PS), trying to elucidate their value as a marker of these diseases. Other studies addressed the potential therapeutic role of CoQ10 in PD and PS. We underwent a systematic review and a meta-analysis of studies measuring tissue CoQ10 concentrations which shows that, compared with controls, PD patients have decreased CoQ10 levels in the cerebellar cortex, platelets, and lymphocytes, increased total and oxidized CoQ10 levels in the cerebrospinal fluid and a non-significant trend toward decreased serum/plasma CoQ10 levels. Patients with multiple system atrophy (MSA) showed decreased CoQ10 levels in the cerebellar cortex, serum/plasma, cerebrospinal fluid, and skin fibroblasts. Patients with Lewy body dementia (LBD) showed decreased cerebellar cortex CoQ10, and those with progressive supranuclear palsy (PSP) had decreased CoQ10 levels in the cerebrospinal fluid. A previous meta-analysis of studies addressing the therapeutic effects of CoQ10 in PD showed a lack of improvement in patients with early PD. Results of the treatment with CoQ10 in PSP should be considered preliminary. The potential role of CoQ10 therapy in the MSA and selected groups of PD patients deserves future studies. [ABSTRACT FROM AUTHOR]

Macrolide antibiotics are important drugs to combat infections. The pharmacokinetics (PK) of these drugs are essential for the determination of their optimal dose regimens, which affect antimicrobial pharmacodynamics and treatment success. For most drugs, the measurement of their concentrations in plasma/serum is the surrogate for drug concentrations in target tissues for therapy. However, for macrolides, simple reliance on total or free drug concentrations in serum/plasma might be misleading. The macrolide antibiotic concentrations of serum/plasma, interstitial fluid (ISF), and target tissue itself usually yield very different PK results. In fact, the PK of a macrolide antibiotic based on serum/plasma concentrations alone is not an ideal predictor for the in vivo efficacy against respiratory pathogens. Instead, the PK based on drug concentrations at the site of infection or ISF provide much more clinically relevant information than serum/plasma concentrations. This review aims to summarize and compare/discuss the use of drug concentrations of serum/plasma, airway ISF, and tissues for computing the PK of macrolides. A better understanding of the PK of macrolide antibiotics based on airway ISF concentrations will help optimize the antibacterial dose regimen as well as minimizing toxicity and the emergence of drug resistance in clinical practice.

It is well known that coenzyme Q10 (CoQ10) has important antioxidant properties. Because one of the main mechanisms involved in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative diseases is oxidative stress, analysis of the concentrations of CoQ10 in different tissues of AD patients and with other dementia syndromes and the possible therapeutic role of CoQ10 in AD have been addressed in several studies. We performed a systematic review and a meta-analysis of these studies measuring tissue CoQ10 levels in patients with dementia and controls which showed that, compared with controls, AD patients had similar serum/plasma CoQ10 levels. We also revised the possible therapeutic effects of CoQ10 in experimental models of AD and other dementias (which showed important neuroprotective effects of coenzyme Q10) and in humans with AD, other dementias, and mild cognitive impairment (with inconclusive results). The potential role of CoQ10 treatment in AD and in improving memory in aged rodents shown in experimental models deserves future studies in patients with AD, other causes of dementia, and mild cognitive impairment.

Several studies investigated diclofenac tissue concentrations using microdialysis (MD). However, thorough evaluations of the optimal MD set‐up for diclofenac are unavailable. Thus, this in vitro MD study aimed to compare different set‐ups to improve quantitative recovery of diclofenac. In forward and reverse in vitro MD experiments with diclofenac at two concentrations (1 and 100 ng/ml), the perfusion solutions physiological saline 0.9% (PS) and human albumin 1% (HSA) were compared using tissue probes (10‐mm membrane) and customized intravenous (iv) probes (30‐mm membrane). Using PS, the mean relative recovery of diclofenac at 1 ng/ml was 1.6% ± 0.04% and 3.12% ± 0.00% with the tissue probe and the iv probe, respectively. The respective mean relative recovery for diclofenac at 100 ng/ml was 0.02% ± 0.01% and 0.21% ± 0.11%. Using HSA, the mean relative recovery was 314% ± 25% (tissue probe) and 1064% ± 97% (iv probe) for diclofenac at 1 ng/ml and 444% ± 91% and 1415% ± 217% for diclofenac at 100 ng/ml. In reverse dialysis using PS, the mean relative loss of diclofenac was 99.2% ± 0.5% (tissue probe) and 95.8% ± 1.7% (iv probe). Using HSA, the mean relative loss was −4.4% ± 7.2% and 0.2% ± 7.5%, respectively. PS and HSA were not suitable perfusion solutions for quantification of absolute diclofenac concentrations. Despite methodological challenges, HSA may be used for comparative experiments or bioequivalence studies. [ABSTRACT FROM AUTHOR]

This study aimed to assess the radiological risk of natural radionuclides (226Ra, 232Th, and 40K) to marine ecosystem biota. The study site in this was the Mediterranean Sea, Cyprus. With the use of the RESRAD-BIOTA (RESidual RADioactivity BIOTA) code, the tissue concentration, external and internal dose rate of aquatic animals and riparian animals were estimated. The total tissue concentrations of the aquatic animals and riparian animals were simulated at 1.14 × 106 Bq/kg (water media) to 0 Bq/kg (sediment media), and 1.33 × 106 Bq/kg (water media) to 9.79 × 101 Bq/kg (sediment media), respectively. The total dose rate for aquatic animals and riparian animals was ranged from 1.94 × 10−2 to 0 Gray per day (Gy/d) and 1.46 × 10−2 to 7.40 × 10−7 Gy/d, respectively. Based on the risk assessment of this study, there is no significant impact due to organisms' exposure to natural radioactivity. Although, further consideration of the exposure levels is required due to the potential effects of protracted low-level ionizing radiation. [ABSTRACT FROM AUTHOR]

Drug development for the central nervous system (CNS) is a complex endeavour with low success rates, as the structural complexity of the brain and specifically the blood-brain barrier (BBB) poses tremendous challenges. Several in vitro brain systems have been evaluated, but the ultimate use of these data in terms of translation to human brain concentration profiles remains to be fully developed. Thus, linking up in vitro-to-in vivo extrapolation (IVIVE) strategies to physiologically based pharmacokinetic (PBPK) models of brain is a useful effort that allows better prediction of drug concentrations in CNS components. Such models may overcome some known aspects of inter-species differences in CNS drug disposition. Required physiological (i.e. systems) parameters in the model are derived from quantitative values in each organ. However, due to the inability to directly measure brain concentrations in humans, compound-specific (drug) parameters are often obtained from in silico or in vitro studies. Such data are translated through IVIVE which could be also applied to preclinical in vivo observations. In such exercises, the limitations of the assays and inter-species differences should be adequately understood in order to verify these predictions with the observed concentration data. This report summarizes the state of IVIVE-PBPK-linked models and discusses shortcomings and areas of further research for better prediction of CNS drug disposition. [ABSTRACT FROM AUTHOR]

Objective The objective of this experiment was to investigate the effects of fat-soluble vitamin injection on plasma and tissue vitamin status in nursery pigs. Methods A total of 16 pigs (initial body weight: 7.15±1.1 kg) were allotted to 2 treatments at d 7 post-weaning. Pigs were fed a corn-soybean meal-based basal diet with no supplemental vitamin A and i.m. injected with 300,000 IU of retinyl palmitate, 900 IU of d-α-tocopherol and 30,000 IU of vitamin D3 with control pigs having no vitamin injection. Blood (d 0, 3, 7, and 14 post-injection) and tissue samples (liver, brain, heart, lung, and muscle; d 7 and 14 post-injection) were collected from pigs. Retinyl palmitate, retinol, and α-tocopherol concentrations were analyzed in plasma and tissues, while plasma was assayed for 25-hydroxycholecalciferol (25-OHD3). Results Plasma retinol and 25-OHD3 concentrations increased by the vitamin injection from d 3 to 14 post-injection (p

Microdialysis is a pharmacokinetic tool that can be advantageous when obtaining tissues' pharmacokinetic information. Since absolute extracellular tissue concentrations are needed in pharmacokinetic studies, calibrating the microdialysis system is necessary. The internal standard method is superior when compared to other calibration methods. However, thorough evaluation of the internal standard is required before it can be used. In vitro experiments and an in vivo study on pigs (n = 8) were conducted to assess the relative recoveries by gain and by loss for piperacillin, both with and without a benzylpenicillin concentration of 5 µg/mL. Furthermore, the in vivo setup allowed for an evaluation of piperacillin cancellous bone and subcutaneous tissue concentrations in a single 8 h dosing interval. Ultra-high performance liquid chromatography (UHPLC) was used to determine piperacillin and benzylpenicillin concentrations. Relative recovery by loss for benzylpenicillin and relative recovery by gain for piperacillin were similar in in vitro and in vivo. Presence of benzylpenicillin did not affect the relative recovery for piperacillin. Relative recovery, pharmacokinetic parameters and f T>MIC were similar when comparing the retrodialysis by drug and the internal standard calibration methods (p > 0.31). Mean f T>MIC (16 µg/mL) for plasma, cancellous bone and subcutaneous tissue were 232 min, 255 min and 295 min, respectively. Our findings suggest that benzylpenicillin is suitable as an internal standard for piperacillin in microdialysis studies. Mean f T>MIC (16 µg/mL) for plasma, cancellous bone, and subcutaneous tissue reached a target of 50% f T>MIC under the investigated conditions (mean range: 52%–66%); however, the target was not obtained in all pigs in all compartments. Moreover, 100% f T>MIC was not obtained in any case, suggesting that different strategies must be taken into consideration if higher targets are employed. [ABSTRACT FROM AUTHOR]

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet. [ABSTRACT FROM AUTHOR]

In an experimental model of low-level and moderate environmental human exposure to cadmium (Cd), it was investigated whether the consumption of a polyphenol-rich Aronia melanocarpa L. berries (chokeberries) extract (AE) may influence the body status of zinc (Zn) and copper (Cu). The bioelements' apparent absorption, body retention, serum and tissue concentrations, total pool in internal organs, excretion, and the degree of binding to metallothionein were evaluated in female rats administered 0.1% aqueous AE or/and Cd in their diet (1 and 5 mg/kg) for 3-24 months. The consumption of AE alone had no influence on the body status of Zn and Cu. The extract administration at both levels of Cd treatment significantly (completely or partially) protected against most of the changes in the metabolism of Zn and Cu caused by this xenobiotic; however, it increased or decreased some of the Cd-unchanged indices of their body status. Based on the findings, it seems that rational amounts of chokeberry products may be included in the daily diet without the risk of destroying Zn and Cu metabolisms; however, their potential prophylactic use under exposure to Cd needs further study to exclude any unfavourable impact of these essential elements on the metabolism. [ABSTRACT FROM AUTHOR]

Carotenoids include C30, C40 and C50 terpenoid-based molecules, many of which constitute coloured pigments. However, >1100 of these are known to occur in nature and only about a dozen are known to play a role in our daily diet. Carotenoids have received much attention due to their proposed health benefits, including reducing the incidence of chronic diseases, such as cardiovascular disease and diabetes. Many of these diseases are characterized by chronic inflammation co-occurring with oxidative stress, characterized by, for example, enhanced plasma F2-isoprostane concentrations, malondialdehyde, and 8-hydroxyguanosine. Though carotenoids can act as direct antioxidants, quenching, for example, singlet oxygen and peroxide radicals, an important biological function appears to rest also in the activation of the body’s own antioxidant defence system, related to superoxide-dismutase, catalase, and glutathione-peroxidase expression, likely due to the interaction with transcription factors, such as nuclear-factor erythroid 2-related factor 2 (Nrf-2). Though mostly based on small-scale and observational studies which do not allow for drawing conclusions regarding causality, several supplementation trials with isolated carotenoids or food items suggest positive health effects. However, negative effects have also been reported, especially regarding beta-carotene for smokers. This review is aimed at summarizing the results from human observational studies/intervention trials targeting carotenoids in relation to chronic diseases characterized by oxidative stress and markers thereof.

The present investigation was undertaken to determine the distribution of 1,2-dichloropropane (DCP) in the blood, liver, kidney, lung, and abdominal fat of rats after oral administration. Male rats were orally administered 62 or 125 mg/kg body weight doses of DCP dissolved in corn oil by gavage, and the concentrations in the blood and tissues were measured. The DCP concentration in the abdominal fat was much greater than in the blood and other tissues. Twenty-four-hr after oral administration, DCP could still be detected in the blood and abdominal fat in the 62-mg/kg group, and in the blood, liver, kidney, lung, and abdominal fat in the 125-mg/kg group. Our results are valuable data pertaining to the pharmacokinetics of DCP and to human health risk assessment of oral exposure to DCP. [ABSTRACT FROM AUTHOR]

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats. [ABSTRACT FROM AUTHOR]

Cadmium, lead, and mercury concentrations were determined in roe deer and wild boar tissues (muscle, liver, kidney) of three different age groups from lowland Croatia. Cadmium concentrations in the examined tissues increased with age in both species, being the highest in the kidney, and higher in roe deer as compared to wild boar. Lead concentration was higher in younger animals in comparison with both older groups. Contrary to the expectations, roe deer tissues revealed mostly higher lead concentrations than those of wild boar. Mercury concentration in the tissues of the animals examined was relatively low and no correlation with age was found. However, mercury concentration was higher in kidney than in liver with both species. Wild boar had higher mercury concentrations in tissues than roe deer in all age groups. Cadmium and mercury concentrations in both species from lowland Croatia are comparable to those given in similar studies in other European countries, while lead concentration was lower in wild boar and higher in roe deer tissues than those in the same species from European countries. From the hygienic point of view, the muscle samples from roe deer and wild boar were edible as the concentrations of cadmium and lead did not exceed the values prescribed by the official regulations. However, cadmium concentration in liver exceeded the prescribed values in one fifth of all samples while lead concentrations were lower than the allowed concentrations. Most kidney samples from both animal species contained cadmium exceeding the recommended concentrations, while lead concentrations in all samples did not exceed the official value regulation. Mercury concentrations are no longer (since 2008) a matter of legislative.

In an experimental model of low-level and moderate environmental human exposure to cadmium (Cd), it was investigated whether the consumption of a polyphenol-rich Aronia melanocarpa L. berries (chokeberries) extract (AE) may influence the body status of zinc (Zn) and copper (Cu). The bioelements’ apparent absorption, body retention, serum and tissue concentrations, total pool in internal organs, excretion, and the degree of binding to metallothionein were evaluated in female rats administered 0.1% aqueous AE or/and Cd in their diet (1 and 5 mg/kg) for 3–24 months. The consumption of AE alone had no influence on the body status of Zn and Cu. The extract administration at both levels of Cd treatment significantly (completely or partially) protected against most of the changes in the metabolism of Zn and Cu caused by this xenobiotic; however, it increased or decreased some of the Cd-unchanged indices of their body status. Based on the findings, it seems that rational amounts of chokeberry products may be included in the daily diet without the risk of destroying Zn and Cu metabolisms; however, their potential prophylactic use under exposure to Cd needs further study to exclude any unfavourable impact of these essential elements on the metabolism.

Plasma disposition and depletion of moxifloxacin were investigated in Japanese quail ( Coturnix japonica) after single intravenous, intramuscular, and oral administration of 5 mg/kg and after intramuscular and oral administration of 5 mg/kg q24h for 5 consecutive days, respectively. Drug concentrations in plasma and tissues were measured by high-performance liquid chromatography with fluorescence detection. After intravenous injection, plasma drug concentration-time curves were best described by a 2-compartment open model. The decline in plasma drug concentration was biexponential with half-lives of 0.3 hours and 2.18 hours for distribution and elimination phases, respectively. Steady-state volume of distribution and total body clearance after intravenous administration were estimated to be 1.12 L/kg and 0.41 L/h per kilogram, respectively. After intramuscular and oral administration of moxifloxacin at the same dose, the peak plasma concentrations were 2.14 and 1.94 μg/mL and were obtained at 1.4 and 1.87 hours, respectively, and the elimination half-lives were 2.56 and 1.97 hours, respectively. The systemic bioavailabilities were 92.48% and 87.94%, respectively. Tissue levels after intramuscular and oral administration were highest in liver and kidneys, respectively, and decreased in the following order: plasma, lungs, and muscle. Moxifloxacin concentrations after intramuscular and oral administration were below the detection limit of the assay in tissues and plasma after 120 hours. [ABSTRACT FROM AUTHOR]

Pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD ratios of a new solvate of enrofloxacin (enrofloxacin hydrochloride-dihydrate; enro-C), were studied in hamsters. Enrofloxacin from Baytril® 5% (enroR) served as the reference preparation. Two groups of 60 Syrian golden hamsters were intramuscularly injected individually with 10 mg/kg of enroR or with enro-C. Tissue and serum samples were obtained for 72 h; enrofloxacin concentrations were determined by HPLC with UV detection. Ninety percent minimum inhibitory concentrations (MIC90) were determined for strains of methicillin-resistant Staphylococcus aureus, Leptospira interrogans, and Escherichia coli. All PK variables were statistically different between groups (P < 0.01). CMAX of enrofloxacin for enro-C was 17.3 µg/mL and it was 2.6 µg/mL for enroR. AUC was considerably higher for enro-C (459.2 µg/mL h vs. 19.9 µg/mL h). There were no statistically significant differences in MIC90 values between enroR and enro-C. Tissue concentrations of enro-C in all cases were higher and remained above the MIC for longer periods than those of enroR. Relevant PK/PD ratios for enrofloxacin (AUC/MIC ≥ 125 and CMAX > MIC = 10-12) are consequently superior for enro-C. Given the outstanding PK/PD ratios of enro-C, this new moiety is proposed as a possible solution when high tissue concentrations of enrofloxacin are necessary. [ABSTRACT FROM AUTHOR]

Bupropion ( BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28-year-old woman who died from a massive lethal overdose with sustained-release bupropion (Wellbutrin® 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry ( LC- MS/ MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable. [ABSTRACT FROM AUTHOR]

The objective of this study was to provide a pharmacokinetic/pharmacodynamic (PK/PD) analysis of moxifloxacin in patients with diabetic foot infections (DFI). The plasma concentration-time courses were determined in 50 DFI patients on day 1 and 3 after intravenous moxifloxacin 400 mg once-daily. A two-compartment population pharmacokinetic model was developed, identifying as covariates total body weight on central and peripheral volume of distribution (V1, V2) and ideal body weight on clearance (CL), respectively. For a 70 kg patient V1 was 68.1 L (interindividual variability, CV: 27.4%), V2 44.6 L, and CL 12.1 L/h (25.6%). Simulations were performed to calculate the probability of target attainment (PTA) for Gram-positive and Gram-negative pathogens with fAUC/MIC targets of ≥30 and ≥100, respectively. PTA was 0.68-1 for susceptible (MIC ≤0.5 mg/L according to EUCAST) Gram-positive, but <0.25 for Gram-negative pathogens with MIC ≥0.25 mg/L. With the exception of the first 24 hours of therapy, obesity affected PTA only marginally. Pharmacokinetic parameters in DFI patients were similar to those reported for healthy volunteers, indicating the appropriateness of the standard dose of moxifloxacin. Overall clinical efficacy has been shown previously, but PTA is limited in a subpopulation infected with formally susceptible Gram-negative pathogens close to the EUCAST breakpoint. [ABSTRACT FROM AUTHOR]

The article reports on a 2015 study of skeletal muscle, liver and kidney samples of young wild boars from Moslavina and Slavonia for cadmium (Cd) content. Based on results, young wild boars can bioindicate environmental pollution with Cd. The article notes that the study's research area has stronger anthropogenic influence than the hunting ground, and that Cd tissue concentration in the samples is lower than the permitted Croatian concentration in food.

Pharmacokinetic profile, tissue concentrations and urine elimination of cephalothin in cats under surgical conditions after a single intravenous dose (30 mg/kg) were studied. Initial plasma concentrations were high [Cp(0), 353.79±118.92 µg/mL], with fast and moderately wide distribution [T1/2(d) 0.14±0.10 h] [V(d(ss)) 0.19±0.03 L/kg] and rapid elimination (ClB, 0.16±0.03 L/h.kg; T1/2, 1.07±0.23 h; MRT, 1.16±0.21 h). Thirty to 60 minutes after intravenous administration, cephalothin tissue concentrations were in the range of 3.73 µg/g (testicle tissue) to 25.63 µg/g (uterus). Tissue/plasma concentrations rate was in a range of 0.04 (testicle) to 0.21 (uterus). Cephalothin urine elimination was 66.49% in the first 6 hours after administration. Cephalothin plasma concentrations remained above a minimum inhibitory concentration (MIC)=1 µg/mL up to 5.5 hours in all the studied cats. However, for MIC=8 µg/mL (MIC breakpoint) this time is reduced to 2.5 hours. This suggests that proper perioperative prophylactic use of cephalothin in cats requires a dose interval not longer than 2 hours. [ABSTRACT FROM AUTHOR]