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Methylnaltrexone prevents morphine‐induced delay in oral‐cecal transit time without affecting analgesia: A double‐blind randomized placebo‐controlled trial
Author(s) -
Yuan ChunSu,
Foss Joseph F.,
O'Connor Michael,
Toledano Alicia,
Roizen Michael F.,
Moss Jonathan
Publication year - 1996
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(96)90117-4
Subject(s) - morphine , medicine , placebo , anesthesia , opioid , analgesic , pharmacology , receptor , alternative medicine , pathology
Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood‐brain barrier and the potential to antagonize the peripherally mediated effects of opioids. The effectiveness of methylnaltrexone in preventing morphine‐induced changes in gastrointestinal motility and transit without affecting analgesia was evaluated in humans. Twelve healthy volunteers were given intravenous placebo, placebo plus 0.05 mg/kg morphine, or 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine. Oral‐cecal transit time was assessed by the pulmonary hydrogen measurement technique, and analgesia was measured with use of the cold‐pressor test. Morphine significantly increased oral‐cecal transit time from 104.6 ± 31.1 minutes (mean ± SD) to 163.3 ± 39.8 minutes ( p < 0.01). Methylnaltrexone prevented 97% of morphine‐induced increase in oral‐cecal transit time (106.3 ± 39.8 minutes; not significant compared with baseline; p < 0.01 compared with morphine alone). Methylnaltrexone did not affect the analgesic effect of morphine on both pain intensity and pain bothersomeness ratings. At a higher dose of morphine (0.1 mg/kg), our preliminary results indicated that 0.45 mg/kg methylnaltrexone also prevented the morphine‐induced delay in oral‐cecal transit time, with no effect on analgesia. Methylnaltrexone may be a useful adjunct to opioids for the relief of opioid‐induced constipation. Clinical Pharmacology & Therapeutics (1996) 59 , 469–475; doi: