The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive

Background: Rifampin (INN, rifampicin), a CYP34A inducer, results in signif icant interactions when coadministered with combination oral contraceptives that contain norethindrone (INN, norethisterone) and ethinyl estradiol (IN N, ethinylestradiol), Little is known about the effects of rifabutin, a rel ated rifamycin. Objectives and Methods: The relative effects of rifampin and rifabutin on t he pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethind rone were evaluated in a prospective, randomized, double-blinded crossover study in 12 premenopausal women who were on a stable oral contraceptive reg imen that contained 35 mu g ethinyl estradiol/l mg norethindrone, Subjects were randomized to receive 14 days of rifampin or rifabutin from days 7 thr ough 21 of their menstrual cycle. After a 1-month washout period (only the oral contraceptives were taken), subjects were crossed over to the other ri famycin, Results: Rifampin significantly decreased the mean area under the plasma co ncentration-time curve from time 0 to 24 hours [AUC(0-24)] of ethinyl estra diol and the mean AUC(0-24) of norethindrone, Rifabutin significantly decre ased the mean AUC(0-24) of ethinyl estradiol and the mean AUC(0-24) of nore thindrone. The effect of rifampin was significantly greater than rifabutin on each AUC(0-24), Despite these changes, subjects did not ovulate (as dete rmined by progesterone concentrations) during the cycle in which either rif amycin was administered, Levels of mean follicle-stimulating hormone increa sed 69% after rifampin. Conclusion: In this study, rifampin (600 mg daily) was a more significant i nducer of ethinyl estradiol and norethindrone clearance than rifabutin (300 mg daily), but neither agent reversed the suppression of ovulation caused by oral contraceptives. The carefully monitored oral contraceptive administ ration and the limited exposure to rifamycins may restrict the application of this study to clinical situations.