MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine.

ABSTRACT: AIMS:The C3435T polymorphism in the human MDR1 gene is associated with lower intestinal P-glycoprotein expression, reduced protein function in peripheral blood cells and higher plasma concentrations of the P-glycoprotein substrate digoxin. Using fexofenadine, a known P-glycoprotein substrate, the hypothesis was tested whether this polymorphism also affects the disposition of other drugs in humans. METHODS:Ten Caucasian subjects homozygous for the wild-type allele at position 3435 (CC) and 10 individuals homozygous for T at position 3435 participated in this study. A single oral dose of 180 mg fexofenadine HCl was administered. Plasma and urine concentrations of fexofenadine were measured up to 72 h using a sensitive LC/MS method. In addition, P-glycoprotein function was assessed using effl

SUBMITTER: Drescher S 

PROVIDER: S-EPMC1874364 | biostudies-literature | 2002 May

REPOSITORIES: biostudies-literature