z-logo
Premium
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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here