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Hepatic and Intestinal Drug Transporters: Prediction of Pharmacokinetic Effects Caused by Drug-Drug Interactions and Genetic Polymorphisms.
MedLine Citation:
PMID:  23140240     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Recent studies of membrane transporters have revealed their importance in determining the pharmacokinetics of transporter substrates. When drugdrug interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the activities of transporters, the pharmacokinetics of transporter substrate drugs is altered; this alteration influences the substrate drugs' subsequent pharmacological or toxicological effects. In predicting these effects quantitatively from in vitro experimental results, we must first determine the contribution of each transporter to the overall elimination process. Furthermore, the accurate estimation of effective inhibitor concentrations at the site of interaction (e.g., intestinal lumen, extracellular and intracellular space of hepatocytes) is challenging. In predicting pharmacogenetic effects, the extrapolation from in vitro observations to in vivo outcomes (e.g., changes in intrinsic activities and/or expression levels) is still evolving. In this review, we describe the current status of, and difficulties inherent in, the accurate prediction of the altered pharmacokinetics caused by transporter-mediated DDIs and pharmacogenetics. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 53 is January 06, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Authors:
Kenta Yoshida; Kazuya Maeda; Yuichi Sugiyama
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Annual review of pharmacology and toxicology     Volume:  -     ISSN:  1545-4304     ISO Abbreviation:  Annu. Rev. Pharmacol. Toxicol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7607088     Medline TA:  Annu Rev Pharmacol Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033 Japan; email: 6.kurabu.pasu@gmail.com.
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