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The Pharmacokinetic and Pharmacodynamic Interactions Between Buprenorphine/Naloxone and Elvitegravir/Cobicistat in Subjects Receiving Chronic Buprenorphine/Naloxone Treatment

2013; Lippincott Williams & Wilkins; Volume: 63; Issue: 4 Linguagem: Inglês

10.1097/qai.0b013e3182961d31

1944-7884

R. Douglas Bruce, Peter Winkle, Joseph M. Custodio, Lilian Xuelian Wei, Martin S. Rhee, Brian P. Kearney, S. Ramanathan, Gerald Friedland,

Pharmacological Effects and Toxicity Studies

Interactions between HIV and opioid-dependence therapies are known to occur. We sought to determine if such interactions occurred between buprenorphine/naloxone and elvitegravir boosted with cobicistat.We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 17 HIV-seronegative subjects stabilized on at least 2 weeks of buprenorphine/naloxone therapy. Subjects underwent baseline and steady state evaluation of the effect of elvitegravir 150 mg once daily boosted with 150 mg once daily of cobicistat (EVG/COBI) on buprenorphine/naloxone parameters. Safety was monitored throughout the study.Compared with baseline values, buprenorphine mean AUCtau (69.0 versus 95.6 hr*ng/mL) and mean Cmax (8.4 versus 9.3 ng/mL) increased significantly in the presence of EVG/COBI. Compared with baseline values, norbuprenorphine mean AUCtau (103.4 versus 163.4 hr*ng/mL) and mean Cmax (6.9 versus 9 ng/mL) also increased significantly after achieving steady state EVG/COBI. Naloxone mean AUCtau (0.57 versus 0.45 hr*ng/mL) and mean Cmax (0.25 versus 0.16 ng/mL) decreased after the addition of EVG/COBI. The AUCtau, Cmax and Ctau of EVG and cobicistat did not significantly differ from historical controls. Opioid withdrawal or overdose was not observed among subjects in this study.The addition of EVG/COBI to stabilized patients receiving buprenorphine/naloxone modestly increased buprenorphine and norbuprenorphine levels without affecting the opioid pharmacodynamics.