Evaluation of drug interactions with P-glycoprotein in drug discovery: In vitro assessment of the potential for drug-drug interactions with P-glycoprotein

Jerome H. Hochman, Masayo Yamazaki, Tomoyuki Ohe, Jiunn H. Lin

Research output: Contribution to journalReview article

95 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)257-273
Number of pages17
JournalCurrent Drug Metabolism
Volume3
Issue number3
DOIs
Publication statusPublished - 2002 Jun 24
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

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