Trapnell Carol Braun, Connolly Margaret, Pentikis Helen, Forbes William P, Bettenhausen Doug K
Clinical Research and Development, ICON Development Solutions, Ellicott City, MD, USA.
Ann Pharmacother. 2007 Feb;41(2):222-8. doi: 10.1345/aph.1H395. Epub 2007 Feb 6.
Rifaximin is an oral rifampin analog, and its activity is targeted within the gastrointestinal tract. Some analogs induce the cytochrome P450 family of oxidative enzymes. Ethinyl estradiol (EE), commonly found in oral contraceptives (OCs), is a known CYP3A4 substrate.
To determine the potential effect of rifaximin on EE and norgestimate pharmacokinetics.
In an open-label, crossover study, healthy females received a single dose of OC (EE 0.07 mg/norgestimate 0.50 mg). Following a 1 week washout period, individuals received rifaximin 200 mg every 8 hours for 3 days, with a single dose of OC administered with the ninth rifaximin dose. During both treatment periods, blood samples were collected periodically for up to 96 hours after each OC dose. Plasma concentration-time profiles and pharmacokinetic parameters were characterized for EE and 2 major metabolites of norgestimate, norgestrel (NG) and 17-deacetyl norgestimate (17-DNGM). A drug-drug interaction was confirmed if the 90% CI for the 2 treatment period comparison was outside the 80-125% limit.
Twenty-six of 28 women completed the study. No differences in pharmacokinetic parameters were observed for EE, NG, or 17-DNGM when a single dose of the OC was administered alone or with rifaximin. In addition, the 90% CI for the bioavailability contrasts (OC alone vs OC with rifaximin) for the maximum plasma concentration, area under the plasma concentration-time curve from zero to the last measurable plasma concentration or to infinity for EE, NG, and 17-DNGM all ranged from 86-118%. These intervals were within the predefined range for equivalence; therefore, no interaction was observed between OC and rifaximin. Rifaximin was well tolerated.
Administration of a 3 day dosing regimen of oral rifaximin was well tolerated and did not alter the pharmacokinetics of a commonly used combination OC containing EE and norgestimate.
利福昔明是一种口服利福平类似物，其活性作用于胃肠道。一些类似物可诱导细胞色素P450氧化酶家族。口服避孕药（OCs）中常见的炔雌醇（EE）是已知的CYP3A4底物。
确定利福昔明对EE和诺孕酯药代动力学的潜在影响。
在一项开放标签的交叉研究中，健康女性接受单剂量OC（EE 0.07 mg/诺孕酯0.50 mg）。经过1周的洗脱期后，个体每8小时接受200 mg利福昔明，共3天，在第9剂利福昔明给药时给予单剂量OC。在两个治疗期内，每次OC给药后定期采集血样，最长至96小时。对EE以及诺孕酯的2种主要代谢产物炔诺孕酮（NG）和17-去乙酰诺孕酯（17-DNGM）的血浆浓度-时间曲线和药代动力学参数进行了表征。如果两个治疗期比较的90%置信区间超出80-125%的范围，则确认存在药物相互作用。
28名女性中有26名完成了研究。单独给予单剂量OC或与利福昔明联合给药时，EE、NG或17-DNGM的药代动力学参数未观察到差异。此外，EE、NG和17-DNGM的最大血浆浓度、从零至最后可测量血浆浓度或至无穷大的血浆浓度-时间曲线下面积的生物利用度对比（单独OC与OC加rifaximin）的90%置信区间均在8
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