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.
RCT Entities:
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.
Authors: H Halawi; P Vijayvargiya; I Busciglio; I Oduyebo; D Khemani; M Ryks; D Rhoten; D Burton; L A Szarka; A Acosta; M Camilleri Journal: Neurogastroenterol Motil Date: 2018-02-06 Impact factor: 3.598
Authors: Anne E Olesen; Debbie Grønlund; Esben B Mark; Klaus Krogh; Jens B Frøkjær; Asbjørn M Drewes Journal: J Neurogastroenterol Motil Date: 2019-10-30 Impact factor: 4.924