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

J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):480-4. doi: 10.1097/QAI.0b013e3182961d31.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / pharmacology*
  • Area Under Curve
  • Buprenorphine / pharmacokinetics*
  • Buprenorphine / pharmacology
  • Buprenorphine / therapeutic use
  • Carbamates / pharmacology*
  • Cobicistat
  • Drug Interactions
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Seronegativity
  • Humans
  • Male
  • Middle Aged
  • Naloxone / pharmacokinetics*
  • Naloxone / pharmacology
  • Naloxone / therapeutic use
  • Narcotic Antagonists / pharmacokinetics*
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / drug therapy
  • Quinolones / pharmacology*
  • Thiazoles / pharmacology*

Substances

  • Anti-Retroviral Agents
  • Carbamates
  • Narcotic Antagonists
  • Quinolones
  • Thiazoles
  • Naloxone
  • Buprenorphine
  • elvitegravir
  • Cobicistat