Influence of ABCB1 gene polymorphisms on the pharmacokinetics of azithromycin among healthy Chinese Han ethnic subjects.
Journal Title: Pharmacological Reports - Year 2009, Vol 61, Issue 5
Abstract
The aim of this study was to evaluate the effects of ABCB1 gene polymorphisms on azithromycin pharmacokinetics in Chinese Han ethnic subjects. In total, 20 healthy volunteers with various ABCB1 genotypes (6 with 2677GG/3435CC, 8 with 2677GT/3435CT, 6 with 2677TT/3435TT) were enrolled. Each was given a single oral dose of 500 mg azithromycin. Plasma concentration was measured for up to 96 h by LC/MS/MS. As shown, C(max) was significantly lower among individuals with 2677TT/3435TT genotype (468.0 +/- 173.4 ng x h/ml) than those with 2677GG/3435CC (911.2 +/- 396.4 ng x h/ml, p = 0.013). However, the t(max) value was higher among subjects with 2677TT/3435TT (2.0 +/- 0.5 h) than those with 2677GT/3435CT (1.6 +/- 0.3 h) or 2677GG/3435CC (1.4 +/- 0.4 h) genotypes (p = 0.068 and p = 0.026, respectively). Furthermore, the AUC(last) tended to be higher among subjects with 2677GG/3435CC than those with 2677GT/3435CT or 2677TT/3435TT genotypes (5000.2 +/- 1610.0 vs. 4558.0 +/- 805.0 vs. 4131.0 +/- 995.1 ng/ml). Our results showed for the first time that azithromycin pharmacokinetics may be influenced by particular polymorphisms of the ABCB1 gene. Individualized dosage regimen design incorporating such information may improve the efficacy of the drug while reducing adverse reactions.
Authors and Affiliations
Xiao-Jing He, Li-Mei Zhao, Feng Qiu, Ya-Xin Sun, Jesse Li-Ling
Keywords
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