The MDR1 (ABCB1) gene polymorphism and its clinical implications

Clinical Pharmacokinetics
Ichiro IeiriKenji Otsubo

Abstract

There has been an increasing appreciation of the role of drug transporters in the pharmacokinetic and pharmacodynamic profiles of certain drugs. Among various drug transporters, P-glycoprotein, the MDR1 gene product, is one of the best studied and characterised. P-glycoprotein is expressed in normal human tissues such as liver, kidney, intestine and the endothelial cells of the blood-brain barrier. Apical (or luminal) expression of P-glycoprotein in these tissues results in reduced drug absorption from the gastrointestinal tract, enhanced drug elimination into bile and urine, and impeded entry of certain drugs into the central nervous system. The clinical relevance of P-glycoprotein depends on the localisation in human tissues (i.e. vectorial or directional movement), the therapeutic index of the substrate drug and the inherent inter- and intra-individual variability. With regard to the variability, polymorphisms of the MDR1 gene have recently been reported to be associated with alterations in disposition kinetics and interaction profiles of clinically useful drugs, including digoxin, fexofenadine, ciclosporin and talinolol. In addition, polymorphism may play a role in patients who do not respond to drug treatment. Moreover, P-...Continue Reading

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