Genetic polymorphisms of drug transporters: pharmacokinetic and pharmacodynamic consequences in pharmacotherapy.
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.
Ieiri
Ichiro
I
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka, 812-8582, Japan. ieiri-ttr@umin.ac.jp
Takane
Hiroshi
H
Hirota
Takeshi
T
Otsubo
Kenji
K
Higuchi
Shun
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004358:Drug Therapy; D006801:Humans; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic
D018528:ATP-Binding Cassette Transporters; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins