Variation of CYP1A2-dependent caffeine metabolism during menstrual cycle in healthy women.
| Autor: | Zaigler M; Institute for Pharmacology, Clinical Pharmacology, Universität zu Köln, Germany., Rietbrock S, Szymanski J, Dericks-Tan JS, Staib AH, Fuhr U |
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| Jazyk: | angličtina |
| Zdroj: | International journal of clinical pharmacology and therapeutics [Int J Clin Pharmacol Ther] 2000 May; Vol. 38 (5), pp. 235-44. |
| DOI: | 10.5414/cpp38235 |
| Abstrakt: | Background and Objectives: The activity of the human cytochrome P450 CYP1A2 is decreased by female sex hormones during pregnancy or treatment with oral contraceptives. However, the influence of menstrual cycle on CYP 1A2 activity is not clear. Methods: CYP1A2 activity was monitored in 15 women (13 with confirmed ovulatory cycles, 2 smokers, age (mean +/- SD) 27.8 +/- 3.8 years, body mass index 23.8 +/- 3.8 kg x m-2) using the specific substrate caffeine (mean doses 149 mg). After a run-in period started one week prior to expected onset of menses, daily saliva samples were taken 7.3 +/- 0.7 hours after caffeine intake throughout the cycle, and caffeine clearance was estimated from the paraxanthine to caffeine ratio therein. Ovulation was confirmed by progesterone serum concentration above 3 ng/ml in the second half of the cycle. Results: Initial (day 2) caffeine clearance (n = 15, geometric mean) was 1.37 ml/min/kg body weight (coefficient of variation (CV) 48%). The ratio of caffeine clearance for the luteal (day -9 to -4 prior to onset of the next menses) to the follicular phase (days 5-10) was (n = 13, point estimate) 1.03 (90% CI 0.95-1.12), indicating that there was no difference in CYP1A2 activity between these cycle phases. The median intraindividual CV in ovulatory cycles (n = 13) was 23% (range 11% to 39%). As an additional finding, there was evidence for long-term fluctuations of CYP1A2 activity in most individuals. Conclusions: A dose adaptation according to the phase of menstrual cycle based on pharmacokinetics is not required for CYP1A2 substrates. |
| Databáze: | MEDLINE |
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