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Transport vs. Metabolism: What Determines the Pharmacokinetics and Pharmacodynamics of Drugs? Insights From the Extended Clearance Model
Author(s) -
PatileaVrana G,
Unadkat JD
Publication year - 2016
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.437
Subject(s) - pharmacokinetics , pharmacodynamics , pharmacology , drug , drug metabolism , transporter , metabolic clearance rate , chemistry , medicine , biochemistry , gene
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.