Effects of Common CYP1A2 Genotypes and Other Key Factors on Intraindividual Variation in the Caffeine Metabolic Ratio: An Exploratory Analysis
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 i...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.12598 |
| Summary: | 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‐naïve 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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| ISSN: | 1752-8054 1752-8062 |