TITLE

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

AUTHOR(S)
Justesen, U. S.; Andersen, Å. B.; Klitgaard, N. A.; Br∅sen, K.; Gerstoft, J.; Petersen, C.
PUB. DATE
February 2004
SOURCE
Clinical Infectious Diseases;2/1/2004, Vol. 38 Issue 3, p426
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
12080882

 

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