Impact of Hepatic Uptake Transporters on Pharmacokinetics and Drug−Drug Interactions: Use of Assays and Models for Decision Making in the Pharmaceutical Industry

The ability to predict hepatic metabolic clearance is a key component in the design and selection of small molecule drug candidates within the pharmaceutical industry. The recognition that metabolism−transporter interplay can influence hepatic metabolic clearance has presented new challenges, both i...

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Bibliographic Details
Published in:Molecular pharmaceutics 2009-12, Vol.6 (6), p.1662-1677
Main Authors: Soars, Mathew G, Webborn, Peter J. H, Riley, Robert J
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Decision Making
Drug Industry - methods
Drug Interactions
Humans
Liver - metabolism
Membrane Transport Proteins - metabolism
Membrane Transport Proteins - physiology
Models, Theoretical
Pharmaceutical Preparations - metabolism
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Summary:The ability to predict hepatic metabolic clearance is a key component in the design and selection of small molecule drug candidates within the pharmaceutical industry. The recognition that metabolism−transporter interplay can influence hepatic metabolic clearance has presented new challenges, both in terms of the creation of experimental systems suitable for an industry setting and also in developing an understanding of the pharmacokinetic concepts that underpin them. This paper reviews the pharmacokinetic principles that govern the kinetics of uptake transporter substrates. In addition, new data are presented from a range of test systems for assessing hepatic drug clearance and the impact of drug−drug interactions (DDIs).
ISSN:1543-8384
1543-8392
DOI:10.1021/mp800246x