title: Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties.
abstract: OBJECTIVE
  Oxycodone DETERx® is an extended-release (ER), microsphere-in-capsule abuse-deterrent-formulation designed to retain its extended-release properties following tampering or misuse (e.g., chewing, crushing). This study assessed the safety and pharmacokinetics of orally administered intact and crushed Oxycodone DETERx® capsules compared with intact and crushed reformulated OxyContin® tablets and crushed immediate-release oxycodone tablets (IR oxycodone).
  
  
  METHODS
  This was a randomized, open-label, active-controlled, cross-over study. Healthy subjects received five oxycodone treatments (40 mg) with a standardized high-fat, high-calorie meal: Oxycodone DETERx® (intact or crushed), OxyContin® (intact or crushed), and IR oxycodone (crushed). Blood samples were collected for assessment of oxycodone plasma concentrations.
  
  
  RESULTS
  Thirty-eight subjects completed the study. Both crushed and intact Oxycodone DETERx® resulted in lower peak plasma concentrations when compared with IR oxycodone. Crushed Oxycodone DETERx® was bioequivalent to intact Oxycodone DETERx® and exhibited a numerically lower Cmax . Also, median Tmax was unchanged by crushing. In contrast, mean peak plasma oxycodone concentrations for crushed OxyContin® were significantly higher compared with intact OxyContin® and were bioequivalent to IR oxycodone. Median Tmax for crushed OxyContin® was the same as IR oxycodone and 3.25 hours shorter than intact OxyContin®.
  
  
  CONCLUSIONS
  These data demonstrate that when crushed and taken orally, Oxycodone DETERx® maintains its EXTENDED-release profile, while crushed OxyContin® shows a pharmacokinetic profile similar to an immediate-release product. These results suggest that Oxycodone DETERx® may be less attractive to illicit drug users compared with existing abuse-deterrent-formulations, while providing a safer option for patients who may unknowingly crush their medication such as those who have difficulty swallowing.
authors.affiliation: Pain Management Center, Englewood Hospital and Medical Center, Englewood, New Jersey, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Gudin
authors.affiliation: Altreos Research Partners Inc, Toronto, Ontario, Canada.
authors.forename: Naama
authors.initials: N
authors.lastname: Levy-Cooperman
authors.affiliation: Collegium Pharmaceutical, Canton, Massachusetts, USA.
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Kopecky
authors.affiliation: Collegium Pharmaceutical, Canton, Massachusetts, USA.
authors.forename: Alison B
authors.initials: AB
authors.lastname: Fleming
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone
keywords: Abuse; Abuse-Deterrent; Extended-Release; Opioids; OxyContin®; Oxycodone DETERx®; Pharmacokinetics; Tamper