Current Concepts in Drug‐Induced Bile Salt Export Pump (BSEP) Interference

J. Gerry Kenna1

1 Safety Science Consultant, Macclesfield, Cheshire
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 23.7
DOI:  10.1002/0471140856.tx2307s61
Online Posting Date:  August, 2014
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Numerous drugs have been shown to inhibit the activity of the Bile Salt Export Pump (BSEP in humans, Bsep in animals), and this is now considered to be one of several mechanisms by which idiosyncratic drug‐induced liver injury (DILI) may be initiated in susceptible patients. The potential importance of BSEP inhibition by drugs has been recognized by the European Medicines Agency and the International Transporter Consortium, who have recommended that it should be evaluated during drug development when evidence of cholestatic liver injury has been observed in nonclinical safety studies or in human clinical trials. In addition, some pharmaceutical companies have proposed evaluation and minimization of BSEP inhibition during drug discovery, when there is a chemical choice, to help reduce DILI risk. The methods that can be used to assess and quantify BSEP inhibition, and key gaps in our current understanding of the relationship between this process and DILI, are discussed. Curr. Protoc. Toxicol.‐23.7.15. © 2014 by John Wiley & Sons, Inc.

Keywords: drug‐induced liver injury; cholestasis; bile salt; ABCB11; drug safety screening

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Table of Contents

  • Role of BSEP Inhibition in Human Cholestatic Liver Injury
  • BSEP Inhibition and Drug‐Induced Liver Injury (DILI)
  • Methods for Evaluation of BSEP Inhibition and their Pitfalls
  • Data and Knowledge Gaps
  • Literature Cited
  • Tables
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Literature Cited

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