BACKGROUND: Studies in healthy volunteers have shown that the recently approved HIV integrase inhibitor dolutegravir has limited drug-to-drug interaction profile. Here we carried out a pharmacokinetic survey in HIV-infected patients given dolutegravir as part of their antiretroviral therapy. METHODS: Dolutegravir plasma trough concentrations were measured in 78 HIV-infected patients given the drug in combination with a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or abacavir/lamivudine. Drug concentrations were assessed by high performance liquid chromatography method with UV-detection. RESULTS: All patients were given dolutegravir at 50 mg once daily, with median trough drug concentrations of 1,096 (664-2,356) ng/ml (interindividual coefficient of variation: 85.3%). Patients given dolutegravir with atazanavir had significantly higher drug concentrations compared with those given darunavir, rilpivirine or abacavir/lamivudine (2,399 [1,929-4,070] versus 738 [552-1,048], 603 [432-1,373] or 1,045 [856-1,115] ng/ml; P<0.001 for all comparisons). By multivariate analyses, only companion antiretroviral drug resulted in significant association with dolutegravir plasma trough concentrations (P=0.012). CONCLUSIONS: Atazanavir coadministration significantly inhibited dolutegravir metabolism, ultimately resulting in a two- to fourfold increase in drug disposition compared with other antiretroviral drugs. This boosting effect of atazanavir could be used to optimize dolutegravir dosing in particular clinical settings.
Dolutegravir plasma concentrations according to companion antiretroviral drug: unwanted drug interaction or desirable boosting effect? / D. Cattaneo, D. Minisci, V. Cozzi, A. Riva, P. Meraviglia, E.G.I. Clementi, M. Galli, C. Gervasoni. - In: ANTIVIRAL THERAPY. - ISSN 1359-6535. - 22:4(2017), pp. 353-356.
|Titolo:||Dolutegravir plasma concentrations according to companion antiretroviral drug: unwanted drug interaction or desirable boosting effect?|
GALLI, MASSIMO (Penultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/17 - Malattie Infettive
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3851/IMP3119|
|Appare nelle tipologie:||01 - Articolo su periodico|