title: Transport vs. Metabolism: What Determines the Pharmacokinetics and Pharmacodynamics of Drugs? Insights From the Extended Clearance Model.
abstract: The well-stirred hepatic clearance model (WSHM) has been expanded to include drug transporters (i.e., extended clearance model [ECM]). However, the consequences of this expansion in understanding when transporters vs. metabolic enzymes will affect the pharmacokinetic (PK) and pharmacodynamic (PD) of drugs remains opaque. Identifying the rate-determining step(s) in systemic or tissue drug PK/PD will allow accurate predictions of drug PK/PD and drug-drug interactions (DDIs). Here, we clarify the implications of the ECM on PK/PD of drugs.
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: G
authors.initials: G
authors.lastname: Patilea-Vrana
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA. jash@uw.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Unadkat
mesh_terms: D001692:Biological Transport; D006801:Humans; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations