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Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non-smoking Healthy Volunteers.


Basic Clin Pharmacol Toxicol. 2012 Nov 21;


Authors: Wang L, Hu Z, Deng X, Wang Y, Zhang Z


Abstract

This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese population. ' Four polymorphisms, CYP1A2*1C (G-3860A), G-3113A, CYP1A2*1F (C-163A) and CYP1A2*1B (C-5347T) 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 CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17X/137X) after administration of 100 mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high-performance liquid chromatography. The activity of CYP1A2 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). CYP1A2*1F polymorphisms were associated with increased CYP1A2 activity in volunteers with -3860G/-3113G/5347C 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. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.

PMID: 23167834 [PubMed - as supplied by publisher]