Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy

Marc Weiner, Naomi Bock, Charles A. Peloquin, William J. Burman, Awal Khan, Andrew Vernon, Zhen Zhao, Stephen Weis, Timothy R. Sterling, Katherine Hayden, Stefan Goldberg

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Abstract

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 (AUC0-∞) increased significantly with dose (rifapentine AUC0-∞: 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, AUC0-∞ 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 AUC0-∞ or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.

Original languageEnglish
Pages (from-to)1191-1197
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume169
Issue number11
DOIs
StatePublished - 1 Jun 2004

Keywords

  • Pharmacokinetics
  • Rifapentine
  • Treatment
  • Tuberculosis

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    Weiner, M., Bock, N., Peloquin, C. A., Burman, W. J., Khan, A., Vernon, A., Zhao, Z., Weis, S., Sterling, T. R., Hayden, K., & Goldberg, S. (2004). Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy. American Journal of Respiratory and Critical Care Medicine, 169(11), 1191-1197. https://doi.org/10.1164/rccm.200311-1612oc