title: Role of Hepatic Drug Transporters in Drug Development.
abstract: 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.
authors.affiliation: Mechanistic Safety and Disposition, Platform Technology and Science, GlaxoSmithKline R&D, Shanghai, China.
authors.forename: Houfu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Projects, Standards & Innovation, Asia Pacific DSAR, Sanofi, Shanghai, China.
authors.forename: Jasminder
authors.initials: J
authors.lastname: Sahi
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control; D055808:Drug Discovery / Q000639:trends*; D004347:Drug Interactions / Q000502:physiology; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D015507:Drugs, Investigational; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: drug development; drug-drug interactions; hepatic drug transporters; pharmacokinetics