期刊
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
卷 12, 期 1, 页码 39-46出版社
WILEY
DOI: 10.1111/cts.12598
关键词
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资金
- National Institutes of Health National Center for Complementary and Integrative Health [U54 AT008909]
- American Beverage Association
- National Center for Complementary & Integrative Health [U54AT008909] Funding Source: NIH RePORTER
The caffeine metabolic ratio is an established marker for cytochrome P450 (CYP) 1A2 activity. Optimal sample size calculation for clinical pharmacokinetic xenobiotic-caffeine interaction studies requires robust estimates of interindividual and intraindividual variation in this ratio. Compared with interindividual variation, factors contributing to intraindividual variation are less defined. An exploratory analysis involving healthy nonsmoking non-naive caffeine drinkers (1-3 cups/day; 12 men, 12 women) administered caffeine (160 mg) on five occasions evaluated the effects of CYP1A2 induction status (based on genotype) and other factors on intraindividual variation in CYP1A2 activity. Results were compared with those from previous studies. Regardless of whether a hyperinducer (CYP1A2*1A/*1F or CYP1A2*1F/*1F) or normal metabolizer (CYP1A2*1A/*1A, CYP1A2*1C/*1F, or CYP1A2*1C*1F/*1C*1F), sex, age, oral contraceptive use by women, and smoking status, intraindividual variation was <= 30%. A value of 30% is proposed for optimal design of pharmacokinetic xenobiotic-caffeine interaction studies. Prospective studies are needed for confirmation.
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