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

B. S. Wong, A. S. Rao, Michael Camilleri, N. Manabe, S. McKinzie, I. Busciglio, D. D. Burton, M. Ryks, A. R. Zinsmeister

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)884-893
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume32
Issue number7
DOIs
StatePublished - Oct 1 2010

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Gastrointestinal Transit
Codeine
Health
Placebos
Ascending Colon
Placebo Effect
Narcotic Antagonists
Therapeutics
methylnaltrexone
Drug Interactions
Healthy Volunteers

ASJC Scopus subject areas

  • Pharmacology (medical)

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The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. / Wong, B. S.; Rao, A. S.; Camilleri, Michael; Manabe, N.; McKinzie, S.; Busciglio, I.; Burton, D. D.; Ryks, M.; Zinsmeister, A. R.

In: Alimentary Pharmacology and Therapeutics, Vol. 32, No. 7, 01.10.2010, p. 884-893.

Research output: Contribution to journalArticle

Wong, B. S. ; Rao, A. S. ; Camilleri, Michael ; Manabe, N. ; McKinzie, S. ; Busciglio, I. ; Burton, D. D. ; Ryks, M. ; Zinsmeister, A. R. / The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. In: Alimentary Pharmacology and Therapeutics. 2010 ; Vol. 32, No. 7. pp. 884-893.
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AU - Manabe, N.

AU - McKinzie, S.

AU - Busciglio, I.

AU - Burton, D. D.

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AU - Zinsmeister, A. R.

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N2 - 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 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.

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