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

Bruce, Robert Douglas MD, MA, MSc*; Winkle, Peter MD; Custodio, Joseph M. PhD; Wei, Lilian Xuelian PhD; Rhee, Martin S. MD; Kearney, Brian P. PhD; Ramanathan, Srinivasan PhD; Friedland, Gerald H. MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2013 - Volume 63 - Issue 4 - p 480–484
doi: 10.1097/QAI.0b013e3182961d31
Clinical Science

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.

*Yale University AIDS Program, New Haven, CT;

Anaheim Clinical Trials, Anaheim, CA; and

Gilead Sciences, Inc, Foster City, CA.

Correspondence to: R. Douglas Bruce, MD, MA, MSc, Yale University AIDS Program, 135 College Street, Suite 323, New Haven, CT 06510 (e-mail: Robert.bruce@yale.edu).

Supported by Gilead Sciences, Inc, and the National Institutes of Health Grant R01DA025932. Gilead is the maker of elvitegravir and cobicistat, which are investigated in this study.

Received January 23, 2013

Accepted April 01, 2013

© 2013 by Lippincott Williams & Wilkins