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疗法圣约翰·沃特（St. John's Wort）（perforatum hyperratum），对左旋甲虫的代谢在剂量方案中用于紧急避孕方案。如果在未受保护的性交后尽快进行紧急避孕，则可以防止怀孕。圣约翰麦芽汁诱导了肝脏中的P450酶系统，因此可能导致某些药物的代谢增加，包括用作紧急避孕的避孕固醇。 这将是三组生殖老年妇女的随机，盲目的临床试验。首先，参与者将在单剂量1.5 mg左甲虫（紧急避孕剂中使用的标准剂量）后进行药代动力学研究。避孕作用将通过孕酮，抑制蛋白A和糖肽水平以1周的间隔估算，直到月经周期结束。然后，参与者将被随机分为三组之一，并服用安慰剂（一组）或圣约翰麦芽汁（两组）6周。药代动力学研究将以相同的标准剂量左旋肺癌紧急避孕剂（在安慰剂和第一圣约翰麦芽汁组中）或左甲虫剂量增加50％（在第二St John's Wort组中）进行重复。避孕作用将通过孕酮，抑制素A和糖肽水平每周进行测量，直到月经周期结束。 安慰剂和活性治疗组之间的药代动力学和生理参数的潜在临床重要差异将通过与基线和基线之间的比较估算。可能会发现可能降低避孕功效的可能效果。结果将用于估计未来的药代动力学 - 剂量动力学研究的参数，这些研究将充分评估相互作用，以及增加剂量以补偿影响的影响。该研究方案将被完善，以在未来的左旋肺癌和其他紧急避孕方案的研究中使用。