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Session 64 Poster Presentations
Drug-Drug Interactions
Session Day and Time: Wednesday 1:30 - 3:30 pm
Room: Hall A


542
Pharmacokinetic Interaction between Rifampin and the Twice-daily Combination of Indinavir and Low-dose Ritonavir in HIV-infected Patients
U. Justesen*1, A. Andersen2, N. Klitgaard3, K. Brosen1, J. Gerstoft2, C. Pedersen3
1Univ of Southern Denmark, Odense, Denmark; 2RigsHospet, Copenhagen, Denmark; and 3Odense Univ Hosp, Denmark

Background: Indinavir (IDV) is primarily metabolized by cytochrome P450 (CYP) 3A4. Rifampin is known to be a strong inducer of CYP3A4, which makes treatment of tuberculosis in HIV-infected patients (pts) receiving IDV complicated. The purpose of this study was to investigate if the inducing effect of rifampin could be overcome by ritonavir (RTV), a strong inhibitor of CYP3A4, when administered in combination with IDV.

Methods: This was a prospective, controlled study with 6 HIV-infected pts receiving the IDV/RTV 800/100 mg regimen in combination with two nucleoside analogues. Pharmacokinetic evaluations of steady-state concentrations of IDV were performed before and after administration of rifampin 300 mg once a day for 4 days. Only pts with IDV C12h > 400 ng/mL could participate. Results were compared with the Wilcoxon signed rank test.

Results:

 

Regimen

IDV C12h (ng/mL)

Median (range)

IDV t½b (h)

Median (range)

IDV/RTV 800/100 mg

837 (406–2154)

2.8 (2.2–2.9)

IDV/RTV 800/100 mg + rifampin

112 (54–258)

1.7 (1.5–2.3)

 

(p = 0.031)

(p = 0.063)

 

Conclusions: There is clinically significant interaction between IDV and rifampin. A dramatic decrease in IDV C12h is seen. It is not possible to administer rifampin together with the IDV/RTV 800/100 mg regimen without risking subtherapeutic concentrations of IDV.