The effect of multiple-dose, oral rifaximin on the pharmacokinetics of intravenous and oral midazolam in healthy volunteers.

Study Objective: To evaluate the potential of rifaximin, an oral nonabsorbed (< 0.4%) structural analog of rifampin, to induce human hepatic and/or intestinal cytochrome P450 (CYP) 3A enzymes, with use of a known CYP3A probe, midazolam.

Design: Prospective, randomized, open-label, two-period, crossover study.

Absence of effect of oral rifaximin on the pharmacokinetics of ethinyl estradiol/norgestimate in healthy females.

Background: 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.

The effect of clarithromycin, fluconazole, and rifabutin on dapsone hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283).

Background: Dapsone hydroxylamine formation is thought to be the cause of the high rates of adverse reactions to dapsone in human immunodeficiency virus (HIV)-infected individuals. Therefore we studied the effect of the commonly coadministered drugs fluconazole, clarithromycin, and rifabutin on hydroxylamine formation in individuals with HIV infection.

Methods: HIV-infected subjects (CD4 + > or =200 cells/mm 3 ) were enrolled in a 2-part (A or B) open-label drug interaction study.

The effect of clarithromycin, fluconazole, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283).

Background: Sulfamethoxazole hydroxylamine formation, in combination with long-term oxidative stress, is thought to be the cause of high rates of adverse drug reactions to sulfamethoxazole in human immunodeficiency virus (HIV)-infected subjects. Therefore the goal of this study was to determine the effect of fluconazole, clarithromycin, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with HIV-1 infection.

Methods: HIV-1-infected subjects (CD4 + count >/=200 cells/mm 3 ) were enrolled in a 2-part (A and B), open-label drug interaction study (Adult AIDS Clinical Trial Group [AACTG] 283).

The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone.

Background: Isotretinoin is a known teratogen, and when it is prescribed to women of childbearing potential, 2 forms of contraception must be used, commonly including hormonal contraception. Although isotretinoin and estradiol are metabolized largely by cytochrome P450 (CYP) 3A4 and glucuronidation, the potential for clinical drug interaction, with subsequent pharmacodynamic impact, has not been evaluated.

Methods: We enrolled 26 healthy women who were to receive isotretinoin for the treatment of severe, recalcitrant nodular acne and who were taking or planning to take oral contraceptives.