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Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective
Author(s) -
Kenna J. Gerry,
Taskar Kunal S.,
Battista Christina,
Bourdet David L.,
Brouwer Kim L.R.,
Brouwer Kenneth R.,
Dai David,
Funk Christoph,
Hafey Michael J.,
Lai Yurong,
Maher Jonathan,
Pak Y. Anne,
Pedersen Jenny M.,
Polli Joseph W.,
Rodrigues A. David,
Watkins Paul B.,
Yang Kyunghee,
Yucha Robert W.
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1222
Subject(s) - bile salt export pump , drug , liver injury , drug discovery , transporter , in vivo , pharmacology , drug development , mechanism (biology) , in vitro toxicology , organic anion transporter 1 , medicine , chemistry , bioinformatics , biology , biochemistry , microbiology and biotechnology , gene , philosophy , epistemology
Bile salt export pump ( BSEP ) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug‐induced liver injury ( DILI ). Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on DILI risk. BSEP inhibition can be quantified using in vitro assays. When interpreting assay data, it is important to consider in vivo drug exposure. Currently, this can be undertaken most effectively by consideration of total plasma steady state drug concentrations (C ss,plasma ). However, because total drug concentrations are not predictive of pharmacological effect, the relationship between total exposure and BSEP inhibition is not causal. Various follow‐up studies can aid interpretation of in vitro BSEP inhibition data and may be undertaken on a case‐by‐case basis. BSEP inhibition is one of several mechanisms by which drugs may cause DILI , therefore, it should be considered alongside other mechanisms when evaluating possible DILI risk.