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24th Annual Meeting
February 13-16, 2008
Orlando, FL
© 2006 American Academy of Pain Medicine
 


Thursday, February 14, 2008
151

Relative Analgesic Potencies of Intranasal Ketamine and Intranasal Morphine Compared to Intravenous Morphine

Edward Liao, Pharm.D., Fred Mermelstein, Ph.D., Curtis Wright, MD, MPH, and Daniel B. Carr, MD. Javelin Pharmaceuticals, Inc., Cambridge, MA, USA

Introduction: Proprietary formulations enabling safe and effective intranasal (IN) delivery of ketamine and morphine are under clinical investigation for the treatment of acute pain. As both may be alternatives to intravenous (IV) morphine, determining their relative potencies to IV morphine may have clinical value. The objective of this analysis was to determine the relative potencies of these three analgesics in a standard pain model.

Methods: Efficacy data was obtained from two dental extraction studies (1,2). Both studies were approved by investigational review boards. The IN ketamine and IN/IV morphine studies were conducted at one common study center, while the morphine study utilized an additional center. Total pain relief over 3 hr [TOTPAR3 by 0-100mm visual analog scale, (VAS)] and 2 hr (TOTPAR2 by 0-4 categorical scale) were the primary efficacy variables in the IN ketamine and IN/IV morphine studies, respectively.

Results: IN ketamine 50mg (n=10), IN morphine 7.5mg (n=45), and IV morphine 7.5mg (n=45) all provided significantly better analgesia than placebo (p<0.05). TOTPAR3 for IN ketamine was 122.3mm∙hr, for a TOTPAR/dose∙hr ratio of 0.82mm/mg∙hr. TOTPAR2 for IN and IV morphine were 2.33 and 3.06 units, respectively. Assuming that 1 categorical unit is equivalent to 25mm on the VAS, the estimated TOTPAR/dose∙hr ratios for IN and IV morphine are 3.88mm/mg∙hr and 5.1mm/mg∙hr, respectively. Normalizing these ratios with IV morphine as the reference, the equianalgesic dose proportions for IN ketamine, IN morphine, and IV morphine are 6.2:1.3:1. The most frequently reported side effects for IN ketamine were “burning sensation/taste in throat”, “tachycardia”, and “hypertension”, while for IN/IV morphine, they were “nausea”, “vomiting”, and “dizziness”.

Conclusions: Based on the observed equianalgesic dose proportions, 30mg IN ketamine and 7.5mg IN morphine, delivered via nasal spray devices, provide analgesia roughly equivalent to 5mg IV morphine in the postoperative molar extraction model of acute moderate-to-severe pain.


References: 1. Christensen K, Rogers E, Green GA, Hamilton DA, Mermelstein F, Liao E, Wright C, Carr DB. Safety and efficacy of intranasal ketamine for acute postoperative pain. Acute Pain. In press.

2. Babul N, Iskold B, Firestone L, Green G, Rogers M. Morphine nasal solution provides analgesic efficacy superior to placebo and comparable to intravenous morphine: results of a randomized, double-blind, placebo-controlled, clinical trial in moderate to severe post-surgical pain. Anesthesiology 2003; 99: A1106.
Funding: Both studies were funded by Javelin Pharmaceuticals.

Edward Liao, Pharm.D.
Conflict of Interest Disclosure: Javelin Pharmaceuticals, Inc., employee

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