1.
Clin Pharmacol Ther
; 100(5): 413-418, 2016 Nov.
Artigo
em Inglês
| MEDLINE
| ID: mdl-27448198
RESUMO
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.