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Pharmacokinetics of Rifapentine at 600, 900, and 1,200 mg during Once-Weekly Tuberculosis Therapy

South Texas Veterans Health Care System, San Antonio, and University of North Texas Health Sciences Center, Fort Worth, Texas; Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia; National Jewish Medical and Research Center, and Denver Public Health Department, Denver, Colorado; Johns Hopkins University School of Medicine, Baltimore, Maryland; Arkansas Department of Health, Little Rock, Arkansas; and Seattle–King County Department of Public Health, Seattle, Washington

Correspondence and requests for reprints should be addressed to Marc Weiner, M.D., Department of Medicine (111F), South Texas Veterans Health Care System, 7400 Merton Minter Boulevard, San Antonio, TX 78229. E-mail: weiner{at}uthscsa.edu

The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration–time curve (AUC_0–) increased significantly with dose (rifapentine AUC_0–: 296, 410, and 477 µg · hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear regression). In multivariate stepwise regression analyses, AUC_0– values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (1 of 35 cases; 3%) and not linked with higher rifapentine AUC_0– or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.

Key Words: pharmacokinetics • rifapentine • treatment • tuberculosis

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