alexa Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial
Nursing

Nursing

Advanced Practices in Nursing

Author(s): Yuan CS, Wei G, Foss JF, OConnor M, Karrison T

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Methylnaltrexone, the first peripheral opioid receptor antagonist, has the potential to prevent or reverse opioid-induced peripherally mediated side effects without affecting analgesia. In previous human trials, we demonstrated that intravenous methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. We also observed that the compound decreased some of the morphine-induced troublesome subjective effects. However, the effects of subcutaneous methylnaltrexone, a more convenient route of administration, have not been evaluated. In this controlled trial, we evaluated the efficacy of subcutanous methylnaltrexone in antagonizing morphine-induced delay in oral-cecal transit time. In addition, opioid-induced unpleasant subjective effects and pharmacokinetics were studied. We observed that in the first group (n = 6) morphine (0.05 mg/kg intravenously) increased the transit time from a baseline level of 85 ± 20.5 min to 155 ± 27.9 min (mean ± S.D., P < 0.01). After 0.1 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 110 ± 41.0 min. In the second group (n = 6), morphine increased the transit time from a baseline level of 98 ± 49.1 min to 140 ± 58.2 min (P < 0.01). After 0.3 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 108 ± 59.6 min (P < 0.05 compared with placebo plus morphine). In addition, subcutaneous methylnaltrexone significantly decreased morphine-induced subjective rating changes. Pharmacokinetic data after subcutaneous drug injection were compared to the data obtained from previous intravenous and oral administrations. Our results suggest that subcutaneous methylnaltrexone may have clinical utility in treating opioid-induced constipation and reducing opioid-induced unpleasant subjective symptoms.

This article was published in American Society for Pharmacology and Experimental Therapeutics and referenced in Advanced Practices in Nursing

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