RIFAMPIN AND RIFABUTIN EFFECT ON COMBINATION ORAL CONTRACEEPTIVES IN HIV WOMEN

利福平和利福布丁对艾滋病毒女性复方口服避孕药的影响

• 批准号: 6114288
• 负责人: PATRICIA A BARDITCH-CROVO
• 金额: $ 2.06万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6114288
• 关键词: HIV infections; clinical research; clinical trial phase I; cytochrome P450; drug interactions; enzyme induction /repression; ethinyl estradiol; female; follicle stimulating hormone; human subject; luteinizing hormone; norethindrone; oral contraceptives; pharmacokinetics; rifabutin; rifamycins

This is a controlled, randomized, Phase I, drug-drug, interaction study to evaluate the effect of rifampin and rifabutin on pharmacokinetics and pharmacodynamics of systemic combined oral contraceptive therapy. Rifabutin and rifampin are drugs that are used in the HIV-infected patient population for the prevention and treatment of mycobacterial diseases. Rifampin is a known enzyme inducer which enhances the metabolism of drugs which are metabolized via the hepatic p450 microsomal enzymes resulting in lower plasma concentrations. Many heterosexual HIV-infected women choose to use oral contraceptives for contraception. It is impossible that systemic levels of ethinyl estradiol and norethindrone are lowered in the presence of rifampin and rifabutin which may render the oral contraceptive ineffective. Although there is some suggestion that rifabutin may have less of an effect on the cytochrome p450 system, it is possible that rifabutin may have enough of any enzyme inducing effect to alter the efficacy of the commonly used combination oral contraceptive pill. This study will provide the first head to head comparison of the ability of rifabutin and rifampin to induce cytochrome p450 function. In addition, this study will provide a paradigm to simultaneously study both the pharmacokinetic and pharmacodynamic effects of a P450 inducer. This study may also provide information of regulatory relevance insomuch as making dosing recommendations in the specific drug labels. The results could have impact on how these drugs are prescribed.

这是一项对照、随机、I期、药物相互作用研究 评价利福平和利福平对药代动力学的影响， 全身联合口服避孕药治疗的药效学。 利福平和利福平是用于艾滋病毒感染者的药物， 用于预防和治疗分枝杆菌感染的患者群体 疾病 利福平是一种已知的酶诱导剂， 通过肝脏p450代谢的药物代谢 微粒体酶导致血浆浓度降低。 许多 异性恋感染艾滋病毒的妇女选择使用口服避孕药， 避孕。 炔雌醇的全身水平和 当存在利福平和利福平时，炔诺酮降低 这可能使口服避孕药无效。 虽然 有迹象表明利福平可能对 细胞色素p450系统，可能利法布里可能有足够的 任何酶诱导作用，以改变常用的 复方口服避孕药 这项研究将提供第一个头对头的能力比较 利福平和利福平诱导细胞色素p450功能。 在 此外，本研究将提供一个范例，同时研究 P450诱导剂的药代动力学和药效学效应。 这项研究还可以提供与监管相关的信息， 在特定的药物标签中提出剂量建议。 的 结果可能会影响这些药物的处方。