Journal Article

Pharmacokinetic Interaction between Rifampin and the Combination of Indinavir and Low-Dose Ritonavir in HIV-Infected Patients

U. S. Justesen, å. B. Andersen, N. A. Klitgaard, K. Brøsen, J. Gerstoft and C. Pedersen

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 38, issue 3, pages 426-429
Published in print February 2004 | ISSN: 1058-4838
Published online February 2004 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/380794
Pharmacokinetic Interaction between Rifampin and the Combination of Indinavir and Low-Dose Ritonavir in HIV-Infected Patients

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Rifampin is an important drug in the treatment of tuberculosis, but administration of rifampin in combination with protease inhibitors is complicated because of drug-drug interactions. A prospective, controlled, multiple-dose study involving 6 HIV-infected patients receiving a combination of indinavir (800 mg) and ritonavir (100 mg) twice a day was performed to evaluate whether the inducing effect of rifampin on the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 could be overcome by the inhibitory effect of ritonavir. Pharmacokinetic evaluations of steady-state concentrations of indinavir and ritonavir were performed before and after administration of rifampin (300 mg every day for 4 days). An 87% reduction (from 837 to 112 ng/mL) in median indinavir and a 94% reduction (from 431 to 27 ng/mL) in median ritonavir concentrations were seen 12 h after the last dose of rifampin was administered (P = .031). These results strongly indicate that the administration of rifampin with a combination of indinavir (800 mg) and ritonavir (100 mg) could lead to subtherapeutic concentrations of indinavir.

Journal Article.  2504 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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