Abstract
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.
Keywords: P-glycoprotein, gender differences, cytochrome P450, drug disposition, male, female, therapeutic outcome
Current Drug Metabolism
Title: Gender Differences in P-Glycoprotein Expression and Function: Effects on Drug Disposition and Outcome
Volume: 10 Issue: 4
Author(s): M. Bebawy and M. Chetty
Affiliation:
Keywords: P-glycoprotein, gender differences, cytochrome P450, drug disposition, male, female, therapeutic outcome
Abstract: 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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Cite this article as:
Bebawy M. and Chetty M., Gender Differences in P-Glycoprotein Expression and Function: Effects on Drug Disposition and Outcome, Current Drug Metabolism 2009; 10 (4) . https://dx.doi.org/10.2174/138920009788498996
DOI https://dx.doi.org/10.2174/138920009788498996 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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