MORENO A, CASADO JL, MARTI-BELDA P, SABIDO R, PEREZ-ELIAS MJ, ANTELA A, DRONDA F, BERMUDEZ E, URIARTE M, MORENO S; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. I-1728.

Ramon Y Cajal Hospital, Madrid, Spain

BACKGROUND: Concomitant use of NNRTI produce a decrease in the pharmacokinetic parameters (PkP) of indinavir (IDV) used at standard doses. The use of dual Ritonavir (RTV)-IDV therapy relies on the enhancing properties of RTV on IDV levels, but the effect of NNRTI on both protease inhibitors PkP is not known. Objective and methods: Comparative analysis of the PkP of RTV and IDV according to NNRTI exposure (n=16, efavirenz in 13) in 27 patients under RTV/IDV dual combination at different doses. The inhibitory quotient (IQ) of each protease inhibitor was defined as previously reported: C trough/protein binding corrected IC95 ratio. RESULTS: At the time of the pharmacokinetic study, all patients had received at least 30 days of NNRTI. Overall, mean IDV and RTV Cmin were 1730 (60-4740) and 456 (56-3470) ngr/ml, with an IQ of 25,44 (0.88-69.7) for IDV and 0.21 (0.02-1.65) for RTV, respectively. When compared to non NNRTI-patients (n=11), adding NNRTI produced non significant decreses in the mean Cmin of IDV (from 1803 to 1623 ngr/ml, 10%) and RTV (from 460 to 449 ngr/ml, 18%), or in the IQ of both protease inhibitors: from 26.52 to 23.87 (10%) for IDV, and from 0.21 to 0.20 (10%) for RTV. According to the bid RTV/IDV schedule, the IDV Cmin were: 1597 (400/400), 2056 (100/800) and 1552 (200/800) ngr/ml, respectively, and the IQ of IDV and RTV, 23.49 and 0.25 (400/400), 30.23 and 0.20 (100/800) and 22.82 and 0.20 (200-800), respectively. CONCLUSIONS: The addition of NNRTI to a dual RTV/IDV combination produces non significant decreases in the inhibitory quotient of both protease inhibitors, regardless their dosing schedule. These data could be useful when designing salvage therapies.

Publication Types:

• Meeting Abstracts

Keywords:

• Antiretroviral Therapy, Highly Active
• Drug Therapy, Combination
• HIV Protease Inhibitors
• Humans
• Indinavir
• Protease Inhibitors
• Reverse Transcriptase Inhibitors
• Ritonavir
• Salvage Therapy
• drug therapy
• efavirenz
• therapy

Other ID:

• GWAIDS0028991

UI: 102268623

From Meeting Abstracts