Genetic polymorphisms of drug transporters: Pharmacokinetic and pharmacodynamic consequences in pharmacotherapy

Ichiro Ieiri, Hiroshi Takane, Takeshi Hirota, Kenji Otsubo, Shun Higuchi

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

There has been increasing appreciation of the role of drug transporters in pharmacokinetic and pharmacodynamic consequences in pharmacotherapy. The clinical relevance of drug transporters depends on the localisation in human tissues (i.e., vectorial movement), the therapeutic index of the substrates and inherent interindividual variability. With regard to variability, polymorphisms of drug transporter genes have recently been reported to be associated with alterations in the pharmacokinetics and pharmacodynamics of clinically useful drugs. A growing number of preclinical and clinical studies have demonstrated that the application of genetic information may be useful in individualised pharmacotherapy for numerous diseases. However, the reported effects of variants in certain drug transporter genes have been inconsistent and, in some cases, conflicting among studies. Furthermore, the incidence of almost all known variants in transporter genes tends to be racially dependent. These observations suggest the necessity of considering interethnic variability before extrapolating pharmacokinetic data obtained in one ethic group to another, especially in the early phase of drug development. This review focuses on the impact of genetic variations in the function of drug transporters (ABC, organic anion and cation transporters) and the implications of these variations for pharmacotherapy from pharmacokinetic and pharmacodynamic viewpoints.

Original languageEnglish
Pages (from-to)651-674
Number of pages24
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume2
Issue number5
DOIs
Publication statusPublished - Dec 1 2006

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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