Association between Common CYP 1 A 2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

• Published in: Basic & clinical pharmacology & toxicology 2013-04, Vol.112 (4), p.257-263
• Main Authors: Wang, Liqing, Hu, Zheyi, Deng, Xun, Wang, Yong, Zhang, Zhongyi, Cheng, Ze‐Neng
• Format: Article
• Language: English
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12038

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.