title: Abuse potential of intravenous oxycodone/naloxone solution in nondependent recreational drug users.
abstract: OBJECTIVE
  Abuse of opioid analgesics has become a public health issue. Some opioid abusers use intravenous administration to increase the magnitude of positive reinforcing effects. Intravenous co-administration of oxycodone with naloxone, an opioid antagonist, may reduce these rewarding effects and discourage abuse. A 2:1 oxycodone:naloxone (OXN) tablet formulation has been studied in the USA for the management of moderate-to-severe chronic pain. Intravenous administration of a 2:1 oxycodone:naloxone solution (sOXN) reflects the oxycodone:naloxone ratio found in laboratory studies of OXN following tampering for intravenous administration. The objective of this study was to characterize abuse-deterrent properties of sOXN.
  
  
  METHODS
  This single-center, double-blind, randomized, placebo-controlled, active-controlled, crossover study enrolled nondependent recreational opioid users with experience using multiple (two or more) routes of administration. Following demonstration that subjects could discern between placebo and oxycodone, 24 eligible male and female subjects were randomized to receive intravenous injections of 0.07 mg/kg oxycodone (OXY), 0.07 mg/kg oxycodone and 0.035 mg/kg naloxone solution (sOXN), or matching placebo over three visits. Pharmacokinetics, pharmacodynamics, safety, and tolerability were assessed at scheduled times up to 8 h post-dose. Parameters were computed and statistically compared among treatments.
  
  
  RESULTS
  Pharmacokinetics were similar between OXY and sOXN. Subjects reported significantly fewer rewarding effects with sOXN compared with OXY; differences between sOXN and placebo were generally not significant. sOXN was well tolerated.
  
  
  CONCLUSIONS
  Significant reductions in drug liking and other subjective effects following administration of sOXN compared with OXY indicate that naloxone concentrations were sufficient to antagonize the effects of oxycodone when abused by the intravenous route of administration in opioid-experienced drug users.
authors.affiliation: Purdue Pharma L.P., One Stamford Forum, 201 Tresser Blvd, Stamford, CT, 06901, USA.
authors.forename: Salvatore V
authors.initials: SV
authors.lastname: Colucci
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Perrino
authors.forename: Megan
authors.initials: M
authors.lastname: Shram
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bartlett
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D012201:Reward; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D004338:Drug Combinations; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone
references.citation: Harm Reduct J. 2011 Oct 19;8:29
references.pmid: 22011626
references.citation: Pain Physician. 2012 Jul;15(3 Suppl):ES9-38
references.pmid: 22786464
references.citation: Drug Alcohol Depend. 2008 Dec 1;98(3):191-202
references.pmid: 18606504
references.citation: Am J Manag Care. 2013 Apr;19(4):295-302
references.pmid: 23725361
references.citation: Behav Pharmacol. 1993 Feb;4(1):3-13
references.pmid: 11224166
references.citation: Harm Reduct J. 2009 May 29;6:8
references.pmid: 19480676
references.citation: Ther Drug Monit. 2008 Aug;30(4):490-6
references.pmid: 18641540
references.citation: Int J Clin Pharmacol Ther. 2012 May;50(5):360-7
references.pmid: 22541841
references.citation: Am J Drug Alcohol Abuse. 1987;13(3):293-308
references.pmid: 3687892
references.citation: Addiction. 2010 Apr;105(4):709-18
references.pmid: 20403021
references.citation: Mayo Clin Proc. 2012 Jul;87(7):683-94
references.pmid: 22766088
references.citation: Psychopharmacology (Berl). 2001 Mar;154(3):230-42
references.pmid: 11351930
references.citation: Eur J Pain. 2009 Jan;13(1):56-64
references.pmid: 18762438