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

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 (AUC(0-infinity)) increased significantly with dose (rifapentine AUC(0- infinity): 296, 410, and 477 microg.hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear regression). In multivariate stepwise regression analyses, AUC(0-infinity) 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-infinity) or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.

• Authors: 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, Tuberculosis Trials Consortium
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 169 Issue 11 Pg. 1191-7 (Jun 01 2004) ISSN: 1073-449X [Print] United States
• PMID: 14962821 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibiotics, Antitubercular
• Drug Combinations
• Isoniazid
• Rifampin
• rifapentine

Topics

• Adult
• Antibiotics, Antitubercular (administration & dosage, adverse effects, pharmacokinetics)
• Area Under Curve
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Combinations
• Female
• Humans
• Isoniazid (administration & dosage, adverse effects)
• Male
• Middle Aged
• Multivariate Analysis
• Mycobacterium tuberculosis (drug effects)
• Prospective Studies
• Rifampin (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Time Factors
• Treatment Outcome
• Tuberculosis, Pulmonary (blood, drug therapy, microbiology)