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

作者：Setnik Beatrice^*; Goli Veeraindar; Levy Cooperman Naama; Mills Catherine; Shram Megan; Smith Ira

来源：Pain Research and Management, 2013, 18(4): E55-E62.

• Abuse potential
• Drug liking
• Intranasal administration
• Morphine
• Naltrexone
• Pharmacodynamic
• Pharmacokinetic

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 (E-max) (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 (E-max 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 E-max 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 (C-max) and median time to C-max 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 C-max was 1497 pg/mL after MSN and median time to C-max 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.

• 出版日期2013-8