IngentaConnect Evaluation of Drug Interactions with P-Glycoprotein in Drug Disco...

Authors: Hochman J.H.; Yamazaki M.; Ohe T.; Lin J.H.

Source: Current Drug Metabolism, Volume 3, Number 3, June 2002 , pp. 257-273(17)

Publisher: Bentham Science Publishers

Abstract:

The pharmacological effects of a drug are highly dependent on the absorption, metabolism, elimination, and distribution of the drug. In the past few years it has become apparent that transport proteins play a major role in regulating the distribution, elimination and metabolism of some drugs. As a consequence of our new understanding of the influence of transport proteins on the pharmacokinetic and pharmacodynamic behavior of drugs, increasing attention has been focused on the potential for drug-drug interactions arising from interactions with drug transport proteins. The efflux transporter P-glycoprotein (P-gp) has received the most attention with regard to its role in restricting drug absorption and distribution and as a potential source for variability in drug pharmacokinetics and pharmacodynamics. This review will focus on the evaluation of drug candidates to assess the potential for drug interactions at the level of P-gp. We will discuss the role of P-gp in drug disposition, the biochemistry of P-gp efflux as it relates to model systems to study drug interactions with P-gp, and the implementation of P-gp assay models within the drug discovery process.

Keywords: p-gp; drug interaction; p-glycoprotein; mdr1

Language: English

Document Type: Review article

DOI: 10.2174/1389200023337559

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Evaluation of Drug Interactions with P-Glycoprotein in Drug Discovery: In Vitro Assessment of the Potential for Drug-Drug Interactions with P-Glycoprotein