ArticleThe Journal of pharmacology and experimental therapeutics2010
Hepatobiliary disposition of troglitazone and metabolites in rat and human sandwich-cultured hepatocytes: use of Monte Carlo simulations to assess the impact of changes in biliary excretion on troglitazone sulfate accumulation.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 57 citations in OpenAlex.
- Development of a Rat Sandwich-Cultured Hepatocytes Model Expressing Functional Human Organic Anion Transporting Polypeptide (OATP) 1B3: A Potential Screening Tool for Liver-Targeting Compounds.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2021Article
- Role of Organic Solute Transporter Alpha/Beta in Hepatotoxic Bile Acid Transport and Drug Interactions.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Farnesoid X Receptor Agonists Obeticholic Acid and Chenodeoxycholic Acid Increase Bile Acid Efflux in Sandwich-Cultured Human Hepatocytes: Functional Evidence and Mechanisms.The Journal of pharmacology and experimental therapeutics · 2018Article
- Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays.BioMed research international · 2017Review
- Prediction of Altered Bile Acid Disposition Due to Inhibition of Multiple Transporters: An Integrated Approach Using Sandwich-Cultured Hepatocytes, Mechanistic Modeling, and Simulation.The Journal of pharmacology and experimental therapeutics · 2016Article
- Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.Journal of pharmaceutical sciences · 2016Review
- Evaluation of Adverse Drug Properties with Cryopreserved Human Hepatocytes and the Integrated Discrete Multiple Organ Co-culture (IdMOC(TM)) System.Toxicological research · 2015Review
- Species differences in hepatobiliary disposition of taurocholic acid in human and rat sandwich-cultured hepatocytes: implications for drug-induced liver injury.The Journal of pharmacology and experimental therapeutics · 2015Article
- Reduced physiologically-based pharmacokinetic model of repaglinide: impact of OATP1B1 and CYP2C8 genotype and source of in vitro data on the prediction of drug-drug interaction risk.Pharmaceutical research · 2014Article
- Hepatocellular exposure of troglitazone metabolites in rat sandwich-cultured hepatocytes lacking Bcrp and Mrp2: interplay between formation and excretion.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- An experimental approach to evaluate the impact of impaired transport function on hepatobiliary drug disposition using Mrp2-deficient TR- rat sandwich-cultured hepatocytes in combination with Bcrp knockdown.Molecular pharmaceutics · 2014Article
- Tacrine sinusoidal uptake and biliary excretion in sandwich-cultured primary rat hepatocytes.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- Hepatic basolateral efflux contributes significantly to rosuvastatin disposition I: characterization of basolateral versus biliary clearance using a novel protocol in sandwich-cultured hepatocytes.The Journal of pharmacology and experimental therapeutics · 2013Article
- Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.Clinical pharmacology and therapeutics · 2013Review
- Combination lopinavir and ritonavir alter exogenous and endogenous bile acid disposition in sandwich-cultured rat hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- A perspective on efflux transport proteins in the liver.Clinical pharmacology and therapeutics · 2012Review
- Novel in vitro-in vivo extrapolation (IVIVE) method to predict hepatic organ clearance in rat.Pharmaceutical research · 2012Article
- Mechanisms underlying differences in systemic exposure of structurally similar active metabolites: comparison of two preclinical hepatic models.The Journal of pharmacology and experimental therapeutics · 2011Article
- Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity.Drug metabolism reviews · 2010Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
This study examined the hepatobiliary disposition of troglitazone (TGZ) and metabolites [TGZ sulfate (TS), TGZ glucuronide (TG), and TGZ quinone (TQ)] over time in rat and human sandwich-cultured hepatocytes (SCH). Cells were incubated with TGZ; samples were analyzed for TGZ and metabolites by liquid chromatography-tandem mass spectrometry. SCH mimicked the disposition of TGZ/metabolites in vivo in rats and humans; TGZ was metabolized primarily to TS and to a lesser extent to TG and TQ. In human SCH, the biliary excretion index (BEI) was negligible for TGZ and TQ, approximately 16% for TS, and approximately 43% for TG over the incubation period; in rat SCH, the BEI for TS and TG was approximately 13 and approximately 41%, respectively. Hepatocyte accumulation of TS was extensive, with intracellular concentrations ranging from 132 to 222 microM in rat SCH; intracellular TGZ concentrations ranged from 7.22 to 47.7 microM. In human SCH, intracellular TS and TGZ concentrations ranged from 136 to 160 microM and from 49.4 to 84.7 microM, respectively. Pharmacokinetic modeling and Monte Carlo simulations were used to evaluate the impact of modulating the biliary excretion rate constant (K(bile)) for TS on TS accumulation in hepatocytes and medium. Simulations demonstrated that intracellular concentrations of TS may increase up to 3.1- and 5.7-fold when biliary excretion of TS was decreased 2- and 10-fold, respectively. It is important to note that altered hepatobiliary transport and the extent of hepatocyte exposure may not always be evident based on medium concentrations (analogous to systemic exposure in vivo). Pharmacokinetic modeling/simulation with data from SCH is a useful approach to examine the impact of altered hepatobiliary transport on hepatocyte accumulation of drug/metabolites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.