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  • Title: The Influence of MDR1 G2677T/a genetic polymorphisms on the pharmacokinetics of repaglinide in healthy Chinese volunteers.
    Author: Xiang Q, Cui YM, Zhao X, Yan L, Zhou Y.
    Journal: Pharmacology; 2012; 89(1-2):105-10. PubMed ID: 22398664.
    Abstract:
    AIMS: The aim of this study was to evaluate the pharmacogenetic variability in the disposition of repaglinide in healthy Chinese subjects. METHODS: A single dose of 2 mg repaglinide was orally administered to 24 healthy Chinese subjects. The serum concentrations of repaglinide were measured by using liquid chromatography/tandem mass spectrometry. We determined the polymorphic alleles of MDR1 C1236T, MDR1 G2677T/A, MDR1 C3435T, CYP3A4*18, OATP1B1 G388A, and OATP1B1 T521C in each subject. RESULTS: The area under the plasma concentration-time curve from time 0 to infinity (AUC((0-inf))) of repaglinide was significantly higher in subjects possessing the MDR1 2677GT and 2677TT alleles than in those with the MDR1 2677GG and 2677TA alleles (p = 0.007). The mean AUCs and peak plasma concentration were higher in subjects with the 521TC allele than in those with the OATP1B1 521TT allele, and the OATP1B1 388A allele is associated with a reduced trend of pharmacokinetic exposure; however, these trends were not statistically significant. The pharmacokinetics of repaglinide was not associated with MDR1 C1236T, MDR1 C3435T, and CYP3A4*18. CONCLUSION: This study shows that the genetic polymorphisms of MDR1 G2677T/A might explain the variability in the pharmacokinetics of repaglinide in the Chinese population.
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