838 ■ The Annals of Pharmacotherapy ■ 2010 May, Volume 44 theannals.com R altegravir, the first licensed HIV in- tegrase inhibitor, is currently ap- proved in several countries for use in combination with other antiretroviral agents for treatment of HIV-1 infection. Raltegravir is active against a wide range of wild-type and multidrug-resistant HIV-1 clinical isolates and, in combina- tion with optimized background therapy, has shown to be safe and effective in achieving immunologic recovery and vi- rologic suppression. 1,2 Pharmacokinetic studies have shown that raltegravir is rapidly absorbed, 3 with steady-state concentrations achieved within 2 days 4,5 ; its metabolism occurs primarily through glucuronidation. 6 Al- though some drugs that induce the rele- vant enzyme, UDP glucuronosyltrans- ferase, may significantly reduce ralte- gravir concentrations, 4,7 this does not apply to commonly used antiretroviral agents. Consequently, raltegravir metab- olism is usually unaffected by concomi- tant administration of nucleoside and nonnucleoside reverse transcriptase in- hibitors (NRTIs, NNRTIs) or protease inhibitors (PIs). 8,9 Available data suggest some interindividual variability for ralte- gravir plasma concentrations. Yilmaz et Raltegravir Plasma Concentrations in Treatment-Experienced Patients Receiving Salvage Regimens Based on Raltegravir With and Without Maraviroc Coadministration Silvia Baroncelli, Paola Villani, Liliana E Weimer, Nicoletta Ladisa, Daniela Francisci, Chiara Tommasi, Vincenzo Vullo, Roberta Preziosi, Stefania Cicalini, Maria Cusato, Clementina M Galluzzo, Marco Floridia, and Mario Regazzi, for the ISS-NIA Group HIV/AIDS Author information provided at end of text. BACKGROUND: Raltegravir and maraviroc represent new, important resources for HIV-infected patients with intolerance or resistance to other antiretroviral agents. The safety and efficacy of both drugs have been investigated, but there is no information on possible pharmacokinetic interactions between these 2 drugs in clinical practice. OBJECTIVE: To evaluate raltegravir plasma concentrations in heavily treatment- experienced patients receiving salvage regimens and explore, in a preliminary assessment, the potential influence of maraviroc coadministration and other cofactors on raltegravir trough concentrations (C trough ). METHODS: Fifty-four HIV-infected patients with triple class (nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, protease inhibitor) treatment experience starting raltegravir 400 mg twice daily, with (n = 11) or without (n = 43) concomitant maraviroc 300 mg twice daily, were evaluated. All regimens included at least 3 drugs of at least 2 different classes. Raltegravir plasma C trough , after at least 1 month of treatment, were analyzed to compare groups of patients taking raltegravir only and raltegravir plus maraviroc. Immunovirological (CD4, HIV-RNA) and clinical data after 6 months of treatment were also collected and described. RESULTS: Raltegravir plasma C trough showed a large variability (range <0.020– 2.47 μg/mL). Median levels were similar in the 2 groups (raltegravir + maraviroc 0.104 μg/mL, range 0.025–0.826; raltegravir 0.090 μg/mL, range <0.020–2.47, p = 0.400). Detectable (>0.02 μg/mL) raltegravir concentrations were observed in all patients receiving raltegravir + maraviroc and in 74% of patients receiving raltegravir alone (p = 0.060). After 6 months of treatment, the 2 groups had similar clinical, virologic, and immunologic conditions. CONCLUSIONS: Coadministration of maraviroc does not seem to have any relevant effects on raltegravir plasma C trough in heavily treatment-experienced patients receiving salvage regimens. Further studies should evaluate the potential additional benefits of maraviroc coadministration in terms of virologic and immunologic response. KEY WORDS: drug interactions, maraviroc, plasma drug concentrations, raltegravir, salvage regimens. Ann Pharmacother 2010;44:838-43. Published Online, 6 Apr 2010, theannals.com, DOI 10.1345/aph.1M688 by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from