A5056589677- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Pharmacogenetics and Drug Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Liver Disease Diagnosis and Treatment
- HIV/AIDS drug development and treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Antibiotics Pharmacokinetics and Efficacy
- Drug Solubulity and Delivery Systems
- Pharmaceutical studies and practices
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Liver Disease and Transplantation
- Antifungal resistance and susceptibility
- Epilepsy research and treatment
- Genetic and Kidney Cyst Diseases
- Hepatitis B Virus Studies
- Amino Acid Enzymes and Metabolism
- Liver Diseases and Immunity
- Analytical Methods in Pharmaceuticals
- Electrolyte and hormonal disorders
- Eicosanoids and Hypertension Pharmacology
- Clinical Nutrition and Gastroenterology
- Gastroesophageal reflux and treatments
University of North Carolina at Chapel Hill
2016-2025
Radboud University Nijmegen
2006-2024
Radboud University Medical Center
2006-2024
Uppsala University
2021
University of Eastern Finland
2019-2021
University of Maryland, Baltimore
2015-2021
Inserm
2021
Centre de Recherche sur l'Inflammation
2021
Université Paris Cité
2021
Centre National de la Recherche Scientifique
2021
The relationship between biliary excretion in sandwich-cultured rat hepatocytes and vivo rats was examined. of seven model substrates 96-h determined by differential cumulative uptake substrate the monolayers preincubated standard buffer (intact bile canaliculi) Ca2+-free (disrupted canaliculi). Biliary quantitated duct-cannulated rats. index substrates, equivalent to percentage retained canalicular networks, consistent with dose excreted from experiments. vitro clearance inulin, salicylate,...
The objective of the present investigation was to examine functional reestablishment polarity in freshly isolated hepatocytes cultured between 2 layers gelled collagen (sandwich configuration). Immunoblot analysis demonstrated that canalicular multispecific organic anion transport protein (multidrug resistance-associated protein, Mrp2) partially maintained day 5 a sandwich configuration. Fluorescein-labeled taurocholate and carboxydichlorofluorescein were excreted into concentrated bile...
Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). The multidrug resistance-associated proteins (MRP) 3 and 4 are postulated be compensatory basolateral efflux transporters when biliary excretion by the salt pump (BSEP) is impaired. BSEP inhibition a risk factor for DILI. This study aimed characterize relationship between MRP3, MRP4, potential drugs. inhibitory effect 88 drugs (100 <i>μ</i>M) on MRP3- MRP4-mediated substrate...
Drug transporters are critically important for the absorption, distribution, metabolism, and excretion (ADME) of many drugs endogenous compounds. Therefore, disruption these pathways by inhibition, induction, genetic polymorphisms, or disease can have profound effects on overall physiology, drug pharmacokinetics, efficacy, toxicity. This white paper provides a review changes in transporter function associated with acute chronic states, describes regulatory affecting expression, identifies...
This white paper examines recent progress, applications, and challenges in predicting unbound total tissue intra/subcellular drug concentrations using vitro preclinical models, imaging techniques, physiologically based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions, case studies illustrate the application of different types data development to support modeling decision making for compounds with transporter-mediated disposition, likely disconnects between systemic...
Previous data suggest that the analgesic effect of morphine may be modulated by P-glycoprotein (P-gp) inhibition. The effects P-gp inhibitor GF120918 on brain distribution and antinociceptive were examined in a rat cerebral microdialysis model. Pretreatment with increased both area under concentration-time curve unbound extracellular fluid (ECF) morphine-associated antinociception. ratio for ECF versus blood was significantly higher GF120918-treated rats compared control (1.21 +/- 0.34 0.47...
Hepatic disposition of 5 (and 6)-carboxy-2′,7′-dichlorofluorescein (CDF) and its diacetate promoiety (CDFDA) was studied in isolated perfused rat livers. Livers from Wistar wild-type multidrug resistance-associated protein (Mrp)2-deficient (TR<sup>−</sup>) rats were with CDF the presence or absence probenecid. Probenecid decreased recovery bile ∼4-fold livers (65 ± 8% versus 15 2% dose over 2 h). In TR<sup>−</sup> rats, not excreted into probenecid perfusate concentrations a...
Bile acid accumulation in hepatocytes due to inhibition of the canalicular bile salt export pump (BSEP/<i>ABCB11</i>) has been proposed as a mechanism for bosentan-induced hepatotoxicity. The observation that bosentan does not induce hepatotoxicity rats, although reported inhibit rat Bsep and cause elevated serum acids, challenges this mechanism. lack could be explained if inhibited hepatocyte uptake well efflux acids. In current study, was found more potent inhibitor...