Co-administration of raltegravir reduces daily darunavir exposure in HIV-1 infected patients
Articolo
Data di Pubblicazione:
2012
Citazione:
Co-administration of raltegravir reduces daily darunavir exposure in HIV-1 infected patients / D. Cattaneo, C. Gervasoni, V. Cozzi, S. Baldelli, S. Fucile, P. Meraviglia, S. Landonio, G. Boreggio, G. Rizzardini, E.G.I. Clementi. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 65:2(2012 Feb), pp. 198-203.
Abstract:
The potential drug-to-drug interaction between darunavir and raltegravir in the setting of HIV infection is a highly debated issue still unresolved. In the present study we have evaluated the pharmacokinetics of darunavir and ritonavir in 53 HIV-1 infected patients with or without concomitant raltegravir administration. The assessment of trough plasma drug concentrations was carried out in all subjects and the potential influence of raltegravir on darunavir and ritonavir disposition, assessed by specific pharmacokinetic evaluations in a subgroup of 25 patients. No significant differences on darunavir and ritonavir plasma trough levels were observed between patients receiving or not raltegravir. Co-administration of raltegravir was, however, associated with a 40% reduction in darunavir C(max) and estimated AUC(0-24), as well a 60% increase in the estimated darunavir clearance compared with values measured in patients not given raltegravir. Notably, this interaction was independent of the dosage of darunavir and not due to effects of raltegravir on the pharmacokinetics of ritonavir. These results should be taken into account when darunavir-based regimens are implemented in the setting of HIV, especially considering that this drug is usually administered at fixed daily dose and no therapeutic drug monitoring is performed in most centres.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Darunavir; Drug-to-drug interactions; HIV; Pharmacokinetics; Raltegravir; Ritonavir
Elenco autori:
D. Cattaneo, C. Gervasoni, V. Cozzi, S. Baldelli, S. Fucile, P. Meraviglia, S. Landonio, G. Boreggio, G. Rizzardini, E.G.I. Clementi
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