title: The pharmacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment.
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.
  
  
  CONCLUSIONS
  The addition of EVG/COBI to stabilized patients receiving buprenorphine/naloxone modestly increased buprenorphine and norbuprenorphine levels without affecting the opioid pharmacodynamics.
authors.affiliation: Yale University AIDS Program, New Haven, CT 06510, USA. Robert.bruce@yale.edu
authors.forename: Robert Douglas
authors.initials: RD
authors.lastname: Bruce
authors.forename: Peter
authors.initials: P
authors.lastname: Winkle
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Custodio
authors.forename: Lilian Xuelian
authors.initials: LX
authors.lastname: Wei
authors.forename: Martin S
authors.initials: MS
authors.lastname: Rhee
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramanathan
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Friedland
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002047:Buprenorphine / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002219:Carbamates / Q000494:pharmacology*; D000069547:Cobicistat; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D018023:HIV Seronegativity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000150:complications / Q000188:drug therapy; D015363:Quinolones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D044966:Anti-Retroviral Agents; D002219:Carbamates; D009292:Narcotic Antagonists; D015363:Quinolones; D013844:Thiazoles; D009270:Naloxone; D002047:Buprenorphine; C509700:elvitegravir; D000069547:Cobicistat