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Medline ® Abstract for Reference 22

of 'Prevention and management of side effects in patients receiving opioids for chronic pain'

Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial.
Yuan CS, Foss JF, O'Connor M, Osinski J, Karrison T, Moss J, Roizen MF
JAMA. 2000 Jan;283(3):367-72.
CONTEXT: Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient.
OBJECTIVE: To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation.
DESIGN: Double-blind, randomized, placebo-controlled trial conducted between May 1997 and December 1998.
SETTING: Clinical research center of a university hospital.
PARTICIPANTS: Twenty-two subjects (9 men and 13 women; mean [SD]age, 43.2 [5.5]years) enrolled in a methadone maintenance program and having methadone-induced constipation.
MAIN OUTCOME MEASURES: Laxation response, oral-cecal transit time, and central opioid withdrawal symptoms were compared between the 2 groups.
RESULTS: The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous methylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for subjects in the methylnaltrexone and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in the methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly greater than the average change in the placebo group (-1.4 [12.0]minutes; P<.001). No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study.
CONCLUSIONS: Our data demonstrate that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid-induced constipation.
Committee on Clinical Pharmacology, Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Ill 60637, USA. cyuan@midway.uchicago.edu