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Effect of the sex‐related MDR1 gene polymorphisms on fexofenadine disposition
Author(s) -
Chung H.,
Yi S.,
Hong K.,
Lim H.,
Chung J.,
Oh D.,
Kim J.,
Cho J.,
Jang I.,
Shin S.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.256
Subject(s) - fexofenadine , genotype , haplotype , medicine , terfenadine , disposition , polymorphism (computer science) , pharmacology , exon , population , endocrinology , biology , genetics , gene , psychology , social psychology , environmental health
There have been contradictory reports about the influence of MDR1 polymorphisms on P‐glycoprotein (PGP) expression and function. We could speculate that sex‐related MDR1 expression difference was the one of reasons of contradictory results. This study was performed to evaluate the MDR1 genotype frequency in the Korean population and impact of genotypes and sex differences on the disposition of the PGP substrate. A total of 232 healthy unrelated Korean volunteers were genotyped for the MDR1 exon 12 1236C>T, exon 21 2677G>T/A and exon 26 3435C>T polymorphism. A single oral dose of 180 mg fexofenadine HCl was administered to 31 healthy subjects, comprised of 9 subjects with 2677GG/3435CC (5 male, 4 female), 12 subjects with 2677GT/3435CT (6 male, 6 female), and 10 subjects with 2677TT/3435TT (6 male, 4 female). Four major haplotypes of C‐A‐C, C‐G‐C, T‐G‐C and T‐T‐T constitute 88.8% of all haplotypes in Korean subjects. Fexofenadine dispositions were not significantly different between gender groups in matched genotype. However, a significant difference in AUC(0–24) were observed in male groups (2677GG/3435CC vs 2677GT/3435CT vs 2677TT/3435TT: 4017 +/‐ 1137 vs 5786 +/‐ 976 vs 5934 +/‐ 2064 ng*hr/mL; P =.038) but not in female groups. We did not identify influence of MDR1 genotype matched sex difference on fexofenadine disposition. Clinical Pharmacology & Therapeutics (2004) 75 , P68–P68; doi: 10.1016/j.clpt.2003.11.256