Transport Vs. Metabolism: What Determines the Pharmacokinetics and Pharmacodynamics of Drugs? Insights From the Extended Clearance Model

Overview

Journal Clin Pharmacol Ther

Publisher Wiley

Specialty Pharmacology

Date 2016 Jul 23

PMID 27448198

Citations 41

Authors

G Patilea-Vrana

J D Unadkat

Affiliations

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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.

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