Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers. (20th December 2012)

• Record Type: Journal Article
• Authors: Wang, Liqing; Hu, Zheyi; Deng, Xun; Wang, Yong; Zhang, Zhongyi; Cheng, Ze‐Neng
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 112:Number 4(2013:Apr.)
• Page Start: 257
• Page End: 263
• Publication Date: 2012-12-20
• Subjects: Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.12038
• Languages: English
• ISSNs: 1742-7835

Abstract

<abstract abstract-type="main" id="bcpt12038-abs-0001"> <title>Abstract</title> <p>This study was designed to investigate the impact of cytochrome <italic>P450 (CYP) 1A2</italic> polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms <italic>CYP1A2*1C</italic> (G‐3860A), G‐3113A, <italic> CYP1A2*1F</italic> (C‐163A) and <italic>CYP1A2*1B</italic> (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 <italic>CYP1A2</italic> 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 <italic>versus</italic> 0.48 ± 0.07, <italic>p </italic>=<italic> </italic>0.016) or the ‐3113 GG genotype (0.35 ± 0.04 <italic>versus</italic> 0.58 ± 0.22, <italic>p </italic>=<italic> </italic>0.037). <italic>CYP1A2*1F</italic> polymorphisms were associated with increased CYP1A2 activity in volunteers with ‐3860G/‐3113G/5347C homozygosity (0.66 ± 0.24 <italic>versus</italic> 0.46 ± 0.05, <italic>p </italic>=<italic> </italic>0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. <italic>CYP1A2</italic> genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but <italic>CYP1A2</italic> gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.</p> </abstract>