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.
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