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Role of Hepatic Drug Transporters in Drug Development
Author(s) -
Liu Houfu,
Sahi Jasminder
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.703
Subject(s) - drug , pharmacology , pharmacokinetics , transporter , drug metabolism , pharmacogenetics , medicine , drug development , in vivo , biology , gene , microbiology and biotechnology , biochemistry , genotype
Hepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug‐drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug‐induced liver injury (DILI), as well as methods for predicting transporter‐mediated pharmacokinetics and DDIs.