ArticleToxicology in vitro : an international journal published in association with BIBRA2010
Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 43 citations in OpenAlex.
- A collagen hydrogel-based 3D Heparg model for enhanced hepatocyte function and assessment of cholestatic drug-induced liver injury.Archives of toxicology · 2026Article
- Review
- Inhibition of canalicular and sinusoidal taurocholate efflux by cholestatic drugs in human hepatoma HepaRG cells.Biopharmaceutics & drug disposition · 2022Article
- Metformin Disrupts Bile Acid Efflux by Repressing Bile Salt Export Pump Expression.Pharmaceutical research · 2020Article
- Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2019Review
- A Change in Bile Flow: Looking Beyond Transporter Inhibition in the Development of Drug-induced Cholestasis.Current drug metabolism · 2019Review
- Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays.BioMed research international · 2017Review
- Monoammonium glycyrrhizinate protects rifampicin- and isoniazid-induced hepatotoxicity via regulating the expression of transporter Mrp2, Ntcp, and Oatp1a4 in liver.Pharmaceutical biology · 2016Article
- Evaluation of Adverse Drug Properties with Cryopreserved Human Hepatocytes and the Integrated Discrete Multiple Organ Co-culture (IdMOC(TM)) System.Toxicological research · 2015Review
- Quantitative NTCP pharmacophore and lack of association between DILI and NTCP Inhibition.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2015Article
- 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
- Use and implications of the harmonic mean model on mixtures for basic research and drug discovery.ACS combinatorial science · 2011Article
- Differential disposition of chenodeoxycholic acid versus taurocholic acid in response to acute troglitazone exposure in rat hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
- Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity.Drug metabolism reviews · 2010Review
- Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans.BioMed research internationalReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatocellular accumulation of bile acids due to inhibition of the canalicular bile salt export pump (BSEP/ABCB11) is one proposed mechanism of drug-induced liver injury (DILI). Some hepatotoxic compounds also are potent inhibitors of bile acid uptake by Na(+)-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1). This study used a cassette dosing approach in rat and human sandwich-cultured hepatocytes (SCH) to determine whether known or suspected hepatotoxic drugs inhibit bile acid transport individually or in combination. [(3)H]-Taurocholate served as the NTCP/BSEP probe substrate. Individually, cyclosporin A and rifampin decreased taurocholate in vitro biliary clearance (Cl(biliary)) and biliary excretion index (BEI) by more than 20% in rat SCH, suggesting that these drugs primarily inhibited canalicular efflux. In contrast, ampicillin, carbenicillin, cloxacillin, nafcillin, oxacillin, carbamazepine, pioglitazone, and troglitazone decreased the in vitro Cl(biliary) by more than 20% with no notable change in BEI, suggesting that these drugs primarily inhibited taurocholate uptake. Cassette dosing (n=2-4 compounds per cassette) in rat SCH yielded similar findings, and results in human SCH were consistent with rat SCH. In summary, cassette dosing in SCH is a useful in vitro approach to identify compounds that inhibit the hepatic uptake and/or excretion of bile acids, which may cause DILI.
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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.