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- Title
The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health.
- Authors
Wong, B. S.; Rao, A. S.; Camilleri, M.; Manabe, N.; McKinzie, S.; Busciglio, I.; Burton, D. D.; Ryks, M.; Zinsmeister, A. R.
- Abstract
Aliment Pharmacol Ther 2010; 32: 884–893 Background The short-term effects of methylnaltrexone (MNTX), a peripherally acting μ-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 t1/2 ( 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.
- Subjects
NALTREXONE; GASTROINTESTINAL agents; PLACEBOS; CODEINE; ANALYSIS of covariance
- Publication
Alimentary Pharmacology & Therapeutics, 2010, Vol 32, Issue 7, p884
- ISSN
0269-2813
- Publication type
Article
- DOI
10.1111/j.1365-2036.2010.04422.x