ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Measures of BSEP Inhibition In Vitro Are Not Useful Predictors of DILI.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Differential effects of metformin-mediated BSEP repression on pravastatin and bile acid pharmacokinetics in humans: A randomized controlled trial.Clinical and translational science · 2022Trial
- A multiparametric in vitro strategy for small molecule drug-induced liver injury risk mitigation in early drug development.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Integration of in vitro and in silico approaches enables prediction of drug-induced liver injury.Archives of toxicology · 2026Article
- Prediction of bile salt export pump inhibition using biomimetic chromatographic descriptors: Integrating membrane affinity and protein binding.ADMET & DMPK · 2026Article
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury.Archives of toxicology · 2025Review
- Mechanisms of drug induced liver injury.Cellular and molecular life sciences : CMLS · 2025Review
- TAK-994 mechanistic investigation into drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Drug-induced cholestasis (DIC) predictions based on in vitro inhibition of major bile acid clearance mechanisms.Archives of toxicology · 2025Article
- Article
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- Identification of reversible OATP1B1 and time-dependent CYP3A4 inhibition as the major risk factors for drug-induced cholestasis (DIC).Archives of toxicology · 2024Article
- Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity.Toxicologic pathology · 2023Review
- Review
- A Unique In Vitro Assay to Investigate ABCB4 Transport Function.International journal of molecular sciences · 2023Article
- Role of Hepatocyte Transporters in Drug-Induced Liver Injury (DILI)-In Vitro Testing.Pharmaceutics · 2022Review
- Inhibition of canalicular and sinusoidal taurocholate efflux by cholestatic drugs in human hepatoma HepaRG cells.Biopharmaceutics & drug disposition · 2022Article
- Role and Regulation of Hepatobiliary ATP-Binding Cassette Transporters during Chemical-Induced Liver Injury.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Challenges and Future of Drug-Induced Liver Injury Research-Laboratory Tests.International journal of molecular sciences · 2022Review
- Analytical and Omics-Based Advances in the Study of Drug-Induced Liver Injury.Toxicological sciences : an official journal of the Society of Toxicology · 2021Review
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2 authors.
Funding
Abstract
Inhibition of the bile salt export pump (BSEP) by a drug has been implicated as a risk factor for a drug's potential to cause drug-induced liver injury (DILI) and is thought to be an important mechanism leading to DILI. For a wide variety of drugs a correlation has been observed between the potency of in vitro BSEP inhibition and its propensity to cause DILI in humans. These findings were interpreted to suggest that BSEP inhibition could be an important mechanism to help explain how some drugs initiate DILI. Because the Biopharmaceutics Drug Disposition Classification System (BDDCS) can be useful in characterizing and predicting some important transporter effects in terms of drug-drug interactions, we evaluated the information provided by BDDCS in order to understand the inhibition propensity of BSEP. Here we analyze the relationship between a compound's ability to inhibit BSEP function and cause liver injury in humans using a compilation of published DILI datasets that have screened for BSEP inhibitors, other hepatic transporters and other mechanism-based toxicity key events. Our results demonstrate that there is little support for in vitro BSEP inhibition being universally DILI predictive. Rather we show that most potent BSEP inhibitors are BDDCS class 2 drugs, which we have demonstrated previously is the BDDCS class most likely to be DILI related. Since BDDCS class is not related to any proposed DILI mechanistic hypotheses, we maintain that if measures of BSEP inhibition alone or together with inhibition of other transporters cannot be differentiated from class 2 assignment, there is no support for in vitro BSEP inhibition being DILI predictive.
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