Current Concepts in Drug‐Induced Bile Salt Export Pump (BSEP) Interference. Issue 1 (7th August 2014)

• Record Type: Journal Article
• Authors: Kenna, J. Gerry
• Editors: Costa, Lucio G; Davila, Julio C.; Lawrence, David A.; Reed, Donald J.
• Is Part Of: Current protocols in toxicology. Volume 61:Issue 1(2014)
• Page Start: 23.7.1
• Page End: 23.7.15
• Publication Date: 2014-08-07
• Subjects: drug‐induced liver injury -- cholestasis -- bile salt -- ABCB11 -- drug safety screening; Toxicology -- Laboratory manuals; Toxicology -- methods; Toxicology; Laboratory Manual; Electronic books; Laboratory manuals; 571.95028
• DOI: 10.1002/0471140856.tx2307s61
• Languages: English
• ISSNs: 1934-9254

Abstract

Abstract: 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 . 61.23.7.1:‐23.7.15. © 2014 by John Wiley & Sons, Inc.