RIFAMPIN AND RIFABUTIN EFFECT ON COMBINATION ORAL CONTRACEEPTIVES IN HIV WOMEN

这是一项对照、随机、第一阶段的药物-药物相互作用研究。 目的：评价利福平和利福平对人体药代动力学的影响。 口服避孕药全身联合治疗的药效学研究。 利福平和利福平是用于艾滋病毒感染者的药物 分枝杆菌防治的患者群体 疾病。利福平是一种已知的酶诱导剂，它可以增强 通过肝脏P450代谢的药物的代谢 微粒体酶导致较低的血浆浓度。许多 感染艾滋病毒的异性恋女性选择口服避孕药 避孕。 可能是全身水平的乙炔雌二醇和 在利福平和利福平存在的情况下，去甲肾上腺素能被降低 这可能会使口服避孕药无效。尽管有 一些建议认为利福布汀可能对 细胞色素P450系统，可能利福布汀有足够的 一种酶的诱导作用，以改变常用的 复方口服避孕药。 这项研究将提供第一次面对面的能力比较 利福平和利福平诱导细胞色素P450功能。在……里面 此外，本研究还将提供一个同步研究的范式 P450诱导剂的药代动力学和药效学效应。 这项研究也可能提供与SO的监管相关的信息 就像在特定的药物标签上提出剂量建议一样。这个 结果可能会对这些药物的处方方式产生影响。 第一部分：在口服避孕药周期的第7天，受试者将 接受促黄体生成素和促卵泡刺激素水平的基线评估，并在24小时内 炔雌二醇和炔诺酮的药动学研究 (NE)。在第8天，在完成24小时档案后，受试者将 开始每24小时服用利福平300毫克，每24小时服用600毫克 已经14天了。在口服避孕药周期的第21天(第14天 利福平或利福平)，受试者将再次接受 黄体生成素和卵泡刺激素水平及其24小时药动学研究 在第7天。 第二部分：经过6周的洗牙期，在他们口腔的第7天 避孕周期，受试者将再次接受基线评估 黄体生成素和卵泡刺激素水平以及EE和NE的24小时药代动力学曲线。 在完成24小时配置文件后，受试者将开始 利福平和利福布汀(未给予任何一种药物)治疗14天 第一部分)。在利福平的第14天，将再次重复简介 或利福布汀(口服避孕药周期的第21天)。 利福平和利福平的给药顺序为 随机化。12名绝经前妇女中有11人处于稳定状态 每日方案正新1-35已完成这项研究。我们预计 于2月初完成研究，并于#年完成数据分析 1997年5月。

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 combine 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 possible that the 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 an 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 in so much as making dosing recommendations in the specific drug labels. The results could have impact on how these drugs are prescribed. PART I: On day 7 of their oral contraceptive pill cycle, subjects will undergo a baseline evaluation of LH and FSH levels and a 24 hour pharmacokinetic profile of ethinyl estradiol (EE) and norethindrone (NE). On day 8, after the 24 hour profile is completed, subjects will start rifabutin 300 mg every 24 hours of rifampin 600 mg every 24 hours for 14 days. on day 21 of their oral contraceptive pill cycle (14th day of rifampin or rifabutin), subjects will again undergo an evaluation of LH and FSH levels and 24 hour pharmacokinetic profile of EE and NE as on day 7. PART II: Following a 6-week wash-out period, on day 7 of their oral contraceptive cycle, subjects will again undergo a baseline evaluation of LH and FSH levels and a 24 hour pharmacokinetic profile of EE and NE. After the 24 hour profile is completed, subjects will then be started on 14 days of rifampin and rifabutin (whichever agent was not given in Part I). Profiles will be repeated again, on the 14th day of rifampin or rifabutin administration (day 21 of the oral contraceptive cycle). The order of administration of rifampin and rifabutin will be randomized. Eleven of 12 pre-menopausal women who have been on a stable daily regimen of ortho-novum 1-35 have completed the study. We expect to complete the study in early February and complete data analysis in May of 1997.