Pollock B G, Wylie M, Stack J A, Sorisio D A, Thompson D S, Kirshner M A, Folan M M, Condifer K A
Geriatric Psychopharmacology Program, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
J Clin Pharmacol. 1999 Sep;39(9):936-40. doi: 10.1177/00912709922008560.
This study was conducted to investigate the effect of therapeutic estrogen on cytochrome P450 1A2-mediated metabolism in postmenopausal women using caffeine as a model substrate. Twelve healthy postmenopausal women underwent estrogen replacement therapy in the form of estradiol (Estrace). Estradiol was initiated at a dose of 0.5 mg a day and titrated to achieve a steady-state plasma concentration of 50 to 150 pg/ml. Caffeine metabolic ratios (CMR; paraxanthine/caffeine) were assessed both before and after 8 weeks of estrogen replacement. For the 12 subjects, there was a mean reduction in CMR of -29.2 +/- 25.0 (p = 0.0019). Consistent with previous results found in younger women, these results indicate that exogenous estrogen in older women may inhibit CYP1A2-mediated caffeine metabolism.
本研究旨在以咖啡因作为模型底物，调查治疗性雌激素对绝经后女性细胞色素P450 1A2介导的代谢的影响。12名健康绝经后女性接受了雌二醇（Estrace）形式的雌激素替代疗法。雌二醇起始剂量为每日0.5毫克，并进行滴定以达到50至150皮克/毫升的稳态血浆浓度。在雌激素替代治疗8周前后均评估了咖啡因代谢率（CMR；副黄嘌呤/咖啡因）。对于这12名受试者，CMR平均降低了-29.2 +/- 25.0（p = 0.0019）。与之前在年轻女性中发现的结果一致，这些结果表明老年女性中的外源性雌激素可能会抑制CYP1A2介导的咖啡因代谢。
