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Gender Differences in P-Glycoprotein Expression and Function: Effects on Drug Disposition and Outcome

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Gender differences in drug concentrations, drug response and toxicity have been attributed to various distinct yet interrelated physiological and molecular mechanisms. Drug transporters and metabolising enzymes play an important role in the xenobiotic cascade and are important regulators of drug disposition at the molecular level. The proposal of a dynamic interplay between drug metabolism and efflux has positioned drug transporters as important mediators of gender disparity in respect to drug disposition and therapeutic response. In examining the effects of gender on drug disposition and response we will specifically direct our focus on the role of the predominant drug transporter, P-glycoprotein. This review focuses on the role of the P-glycoprotein as a molecular mediator of gender differences in both drug exposure and response. Differences in transporter expression and function will be discussed together with the molecular basis for the observed difference in drug exposure between the sexes. Gender differences affecting transporter expression and function at the effect compartment and the effect of this on drug response will also be discussed.

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Keywords: P-glycoprotein; cytochrome P450; drug disposition; female; gender differences; male; therapeutic outcome

Document Type: Research Article

Publication date: May 1, 2009

More about this publication?
  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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