The pharmacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment.

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: The addition of EVG/COBI to stabilized patients receiving buprenorphine/naloxone modestly increased buprenorphine and norbuprenorphine levels without affecting the opioid pharmacodynamics.