alexa In vitro-in vivo extrapolation of transporter-mediated clearance in the liver and kidney.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Kusuhara H, Sugiyama Y

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Abstract Transporters govern drug movement into and out of tissues, thereby playing an important role in drug disposition in plasma and to the site of action. The molecular cloning of such transporters has clarified the importance of members of the solute carrier family, such as OATP/SLCO, OCT/SLC22, OAT/SLC22, and MATE/SLC47, and the ATP-binding cassette transporters, such as P-glycoprotein/ABCB1, MRPs/ABCC, and BCRP/ABCG2. Elucidation of molecular characteristics of transporters has allowed the identification of transporters as mechanisms for drug-drug interactions, and of interindividual differences in drug dispositions and responses. Cumulative studies have highlighted the cooperative roles of uptake transporters and metabolic enzymes/efflux transporters. In this way, the concept of a rate-limiting process in hepatic/renal elimination across epithelial cells has developed. This review illustrates the concept of the rate-limiting step in the hepatic elimination mediated by transporters, and describes the prediction of the in vivo pharmacokinetics of drugs whose disposition is determined by transporters, based on in vitro experiments using pravastatin as an example. This review also illustrates the transporters regulating the peripheral drug concentrations.
This article was published in Drug Metab Pharmacokinet and referenced in Journal of Bioequivalence & Bioavailability

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