The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health.
BACKGROUND
The short-term effects of methylnaltrexone (MNTX), a peripherally acting mu-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear.


OBJECTIVE
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).


CONCLUSIONS
Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health.
Wong
B S
BS
Mayo Clinic, Rochester, MN 55905, USA.
Rao
A S
AS
Camilleri
M
M
Manabe
N
N
McKinzie
S
S
Busciglio
I
I
Burton
D D
DD
Ryks
M
M
Zinsmeister
A R
AR
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D003061:Codeine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D055815:Young Adult
D000701:Analgesics, Opioid; D004338:Drug Combinations; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu; C032257:methylnaltrexone; D009271:Naltrexone; D003061:Codeine