Pharmacokinetics of rifapentine in subjects seropositive for the human immunodeficiency virus: a phase I study

Rifapentine is undergoing development for the treatment of pulmonary tuberc ulosis. This study was conducted to characterize the single-dose pharmacoki netics of rifapentine and its 25-desacetyl metabolite and to assess the eff ect of food on the rate and extent of absorption in participants infected w ith human immunodeficiency virus (HIV). Twelve men and four women, mean age , 38.6 +/- 6.9 years, received a single 600-mg oral dose of rifapentine in an open-label, randomized two-way, complete crossover study. Each volunteer received rifapentine following a high-fat breakfast or during a fasting pe riod. Serial blood samples were collected for 72 h and both:rifapentine and its metabolite were assayed by a validated high-performance liquid chromat ography method. Pharmacokinetics of rifapentine and 25-desacetylrifapentine were determined by noncompartmental methods. Mean (+/- the standard deviat ion) maximum concentrations of rifapentine in serum and areas under the cur ve from time zero to infinity following a high-fat breakfast were 14.09 +/- 2.81 and 373.63 +/- 78.19 mu g/ml, respectively, and following a fasting p eriod they were 9.42 +/- 2.67 and 256.10 +/- 86.39 mu g . h/ml, respectivel y. Pharmacokinetic data from a previously published healthy volunteer study were used for comparison. Administration of rifapentine with a high-fat br eakfast resulted in a 51% increase in rifapentine bioavailability, an effec t also observed in healthy volunteers, Although food increased the exposure of these patients to rifapentine, the infrequent dosing schedule for the t reatment of tuberculosis (e.g., once- or twice-weekly dosing) would be unli kely to lead to accumulation. Additionally, autoinduction has been previous ly studied and has not been demonstrated with this compound, unlike with ri fabutin and rifampin. Rifapentine was well tolerated by HIV-infected study participants. The results of our study suggest that no dosage adjustments m ay be required for rifapentine in HIV-infected patients (Centers for Diseas e Control and Prevention classification Al, A2, B1, or B2) undergoing treat ment for tuberculosis.