Randomized, Double-Blind, Placebo-Controlled Study of the Abuse Potential of Different Formulations of Oral Oxycodone

Authors


  • Conflict of interest: Dr. Webster: Consultant to and on the Advisory Board of King Pharmaceuticals; Dr. Bath: None; Dr. Medve: None; Dr. Marmon: None; Mr. Stoddard: None.

  • Role of funding source: This research was supported by a research grant from King Pharmaceuticals. King Pharmaceuticals did not contribute to the design, execution, analysis, or writing of the study.

  • Contributors:

  • Dr. Webster: Wrote the protocol, conducted the study, analyzed data, and wrote the article

  • Dr. Bath: Contributed to protocol design, conducted the study, and analyzed data

  • Dr. Medve: Contributed to the protocol design and analyzed data

  • Dr. Marmon: Contributed to protocol design and conducted statistical analysis

  • Mr. Stoddard: Reviewed results and performed statistical analysis

  • All of the above individuals reviewed the article critically and provided final approval.

Lynn R. Webster, MD, Lifetree Clinical Research, 3838 South 700 East, Suite 202, Salt Lake City, UT 84106, USA. Tel: 801-261-4988; Fax: 801-261-8389; E-mail: lynnw@lifetreepain.com.

Abstract

Objective.  The objective of this study was to evaluate the pharmacokinetics and abuse potential of different formulations of oxycodone.

Design.  The participants completed an 8-day, placebo-controlled trial with four phases: naloxone challenge, double-blind drug discrimination, double-blind abuse liability, and discontinuation.

Subjects.  Nineteen healthy, male, recreational drug abusers participated in this study.

Interventions.  The participants were administered different doses and formulations of oxycodone (40 mg immediate release [IR], 40 mg controlled release [CR], crushed 40 mg CR, and 80 mg CR) to evaluate pharmacokinetic parameters and ratings of drug liking and high.

Outcome Measures.  Pharmacokinetic parameters were determined over a 12-hour dosing interval. The primary pharmacodynamic endpoints were two questions from the Drug Effects Questionnaire (“Do you like the drug?” and “How high are you now?”).

Results.  Maximal plasma concentrations and area under the curve determinations were similar for 40 mg IR, crushed 40 mg CR, and 80 mg CR, which were all greater than 40 mg CR. For drug liking and high, the maximal effect and area under the effect curve were similar for the three formulations, which were all greater than 40 mg CR. The dose required to produce comparable reports of drug liking and high was approximately twofold greater for the CR vs IR formulation. When the 40 mg CR tablet was crushed, the pharmacokinetic and pharmacodynamic profile was similar to the 40 mg IR formulation. Adverse events were consistent with opioid administration.

Conclusions.  Intact, orally administered oxycodone CR produced less drug liking and high than IR oxycodone, and required approximately twofold greater doses to produce subjective effects comparable to IR oxycodone.

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