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Pain Research and Management
Volume 18 (2013), Issue 4, Pages e55-e62
http://dx.doi.org/10.1155/2013/952082
Original Article

Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

Beatrice Setnik,1 Veeraindar Goli,1,2 Naama Levy-Cooperman,3 Catherine Mills,3 Megan Shram,3,4 and Ira Smith3

1Pfizer Inc, Cary, USA
2Duke University Medical Center, Durham, North Carolina, USA
3INC Research, University of Toronto, Toronto, Ontario, Canada
4Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

OBJECTIVE: To evaluate the pharmacodynamic (PD) effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN) capsules compared with controlled-release morphine sulfate (MS) and placebo when crushed and administered intranasally.

METHODS: The present study was a randomized, double-blinded, placebo-controlled, single-dose (30 mg), three-way crossover study in healthy, nondependent recreational opioid users. PD measures included assessment of subjective drug effects using visual analogue scales (VAS) ranging from 0 to 100 and assessments of pupil diameter. Blood samples were collected for pharmacokinetic analyses.

RESULTS: Both MS and MSN showed significantly higher PD values compared with placebo. MSN showed significantly lower scores for drug liking and high VAS scores on both mean peak effect (Emax) (69.6 and 55.2, respectively) and in area under the effect curve over 2 h (86.3 and 66.7, respectively) following dosing compared with MS (Emax 87.6 and 86.6, respectively; area under the curve over 2 h 120.6 and 132.9, respectively; P<0.001). MSN showed significantly lower Emax for all other positive subjective effects (good drug effects, overall drug liking, and take drug again VAS scores) compared with MS (P<0.001). Peak minimum pupil diameter was significantly larger for MSN than MS (P=0.002). Mean peak plasma concentration (Cmax) and median time to Cmax for morphine following administration of MSN and MS were similar (27.3 ng/mL and 0.57 h versus 27.7 ng/mL and 0.6 h, respectively). Naltrexone mean Cmax was 1497 pg/mL after MSN and median time to Cmax was 0.55 h.

CONCLUSIONS: When crushed and administered intranasally, MSN was associated with significantly lower ratings of drug liking and other positive subjective effects compared with MS.