Acf. Keung et al., Pharmacokinetics of rifapentine in subjects seropositive for the human immunodeficiency virus: a phase I study, ANTIM AG CH, 43(5), 1999, pp. 1230-1233
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.