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The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health.

Author(s): Wong BS, Rao AS, Camilleri M, Manabe N, McKinzie S, Busciglio I, Burton DD, Ryks M, Zinsmeister AR

Affiliation(s): Mayo Clinic, Rochester, MN 55905, USA.

Publication date & source: 2010-10, Aliment Pharmacol Ther., 32(7):884-93.

Publication type: Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

BACKGROUND: The short-term effects of methylnaltrexone (MNTX), a peripherally acting mu-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. AIM: To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. METHODS: In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. RESULTS: Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t(1/2) (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). CONCLUSION: Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health.

Page last updated: 2010-10-05

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