title: Transporter-mediated drug interactions: clinical implications and in vitro assessment.
abstract: Although they are less frequently compared with the reported cases of CYP-mediated drug interactions, clinically significant transporter-mediated drug interactions, which are mainly based on efflux transporter or P-glycoprotein data, have been reported. Unlike the CYP-mediated drug interactions that can be readily defined by inhibition or induction of CYP enzymes, the evidence for the so-called transporter-mediated drug interactions is often less conclusive. The difficulty in defining transporter-mediated drug interactions is due mainly to the interplay between transporters and drug-metabolizing enzymes in drug disposition, and the lack of specific and potent inhibitors for each transporter and enzyme. An important lesson learned from animal studies is that transporter inhibition has a much greater impact on the tissue distribution of drugs than on the systemic exposure of drugs measured in plasma. The potential risk of transporter-mediated drug interactions might be underestimated if only plasma concentrations are monitored.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA. jiunn_lin@merck.com
authors.forename: Jiunn H
authors.initials: JH
authors.lastname: Lin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008874:Midazolam / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D012293:Rifampin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D008874:Midazolam; D007654:Ketoconazole; D012293:Rifampin