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Association between Common CYP 1 A 2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers
Author(s) -
Wang Liqing,
Hu Zheyi,
Deng Xun,
Wang Yong,
Zhang Zhongyi,
Cheng ZeNeng
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12038
Subject(s) - theophylline , genotype , cyp1a2 , pharmacology , cyp2c9 , metabolism , caffeine , cytochrome p450 , chemistry , population , cyp2d6 , pharmacokinetics , haplotype , medicine , endocrinology , biology , biochemistry , gene , environmental health
This study was designed to investigate the impact of cytochrome P 450 ( CYP ) 1 A 2 polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms CYP 1 A 2*1 C ( G ‐3860 A ), G ‐3113 A , CYP 1 A 2*1 F ( C ‐163 A ) and CYP 1 A 2*1 B ( C ‐5347 T ) were screened in 238 unrelated male volunteers. Then, a single oral 200‐mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP 1 A 2 genotype. CYP 1 A 2 activities were evaluated by plasma 1,7‐dimethylxanthine/caffeine ratios (17 X /137 X ) after administration of 100‐mg caffeine. The plasma concentrations of theophylline, 17 X and 137 X were determined by high‐performance liquid chromatography. The activity of CYP 1 A 2 was lower in volunteers with the ‐3113 AA genotype compared with those with the ‐3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the ‐3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP 1 A 2*1 F polymorphisms were associated with increased CYP 1 A 2 activity in volunteers with ‐3860 G /‐3113 G /5347 C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP 1 A 2 genetic polymorphisms influenced CYP 1 A 2 enzyme activity as measured by caffeine, but CYP 1 A 2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.