St. John's Wort Effects on Levonorgestrel

圣约翰草对左炔诺孕酮的影响

• 批准号: 7070056
• 负责人: PATRICIA A. MURPHY
• 金额: $ 21.9万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7070056
• 关键词: St Johns wort; alternative medicine; clinical research; dosage; drug metabolism; human subject; inhibin; levonorgestrel; medicinal plants; menstrual cycle; oral contraceptives; pharmacokinetics; progesterone

DESCRIPTION (provided by applicant): This study will evaluate the effects of chronic use of a common herbal remedy, St. John's Wort (Hypericum perforatum), on metabolism of levonorgestrel in a dosing regimen for emergency contraception. Emergency contraception, if taken soon after unprotected intercourse, prevents pregnancy. St. John's Wort induces the P450 enzyme system in the liver, and as such may cause increased metabolism of certain drugs, including contraceptive steroids used as emergency contraception. This will be a randomized, blinded, clinical trial of three groups of reproductive-aged women. First, participants will have pharmacokinetic studies done after a single dose of 1.5 mg levonorgestrel, the standard dose used in emergency contraception. Contraceptive effects will be estimated via progesterone, inhibin A, and glycodelin levels done at 1-week intervals until the end of the menstrual cycle. Participants will be then randomized to one of three groups and take either placebo (one group) or St. John's Wort (two groups) for 6 weeks. The pharmacokinetic studies will be repeated with either the same standard dose of levonorgestrel emergency contraception (in the placebo and first St. John's Wort groups) or after a levonorgestrel dose that has been increased by 50% (in the second St John's Wort group). Contraceptive effects will be measured by progesterone, inhibin A, and glycodelin levels at weekly intervals until the end of the menstrual cycle. Potentially clinically important differences in pharmacokinetic and physiologic parameters between placebo and active treatment groups will be estimated by comparisons to baseline and between groups. Possible effects that may reduce contraceptive efficacy will be identified. Results will be used to estimate parameters for future pharmacokinetic-pharmacodynamic studies that will fully assess the interaction, as well as effects of increasing dosage to compensate for effects. The study protocol will be refined for use in future studies of levonorgestrel and other emergency contraceptive regimens.

描述（由申请人提供）：本研究将评估长期使用常见草药圣约翰草（贯叶连翘）对紧急避孕给药方案中左炔诺孕酮代谢的影响。如果在无保护的性交后立即服用紧急避孕药，可以防止怀孕。圣约翰草会诱导肝脏中的 P450 酶系统，因此可能会导致某些药物的代谢增加，包括用作紧急避孕的避孕类固醇。 这将是一项针对三组育龄妇女的随机、盲法临床试验。首先，参与者将在单剂量服用 1.5 毫克左炔诺孕酮（紧急避孕药中使用的标准剂量）后进行药代动力学研究。避孕效果将通过每 1 周一次的黄体酮、抑制素 A 和甘油磷脂水平进行评估，直至月经周期结束。然后，参与者将被随机分为三组中的一组，并服用安慰剂（一组）或圣约翰草（两组）为期 6 周。药代动力学研究将使用相同标准剂量的左炔诺孕酮紧急避孕药（安慰剂组和第一组圣约翰草组）或左炔诺孕酮剂量增加 50% 后（第二组圣约翰草组）重复进行。避孕效果将通过每周一次的黄体酮、抑制素 A 和甘油磷脂水平进行测量，直至月经周期结束。 将通过与基线和组间比较来估计安慰剂组和活性治疗组之间药代动力学和生理参数的潜在临床重要差异。将确定可能降低避孕功效的可能影响。结果将用于估计未来药代动力学-药效学研究的参数，这些研究将充分评估相互作用以及增加剂量以补偿效应的影响。该研究方案将进行完善，以用于未来左炔诺孕酮和其他紧急避孕方案的研究。