TY - JOUR
T1 - Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy
AU - Weiner, Marc
AU - Bock, Naomi
AU - Peloquin, Charles A.
AU - Burman, William J.
AU - Khan, Awal
AU - Vernon, Andrew
AU - Zhao, Zhen
AU - Weis, Stephen
AU - Sterling, Timothy R.
AU - Hayden, Katherine
AU - Goldberg, Stefan
PY - 2004/6/1
Y1 - 2004/6/1
N2 - 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.
AB - 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.
KW - Pharmacokinetics
KW - Rifapentine
KW - Treatment
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=2542452030&partnerID=8YFLogxK
U2 - 10.1164/rccm.200311-1612oc
DO - 10.1164/rccm.200311-1612oc
M3 - Article
C2 - 14962821
AN - SCOPUS:2542452030
SN - 1073-449X
VL - 169
SP - 1191
EP - 1197
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 11
ER -