Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study.
background & aims: Opiate bowel dysfunction is a significant clinical problem. Our aim was to evaluate the ability of a peripheral mu-opioid antagonist, alvimopan, to reverse the effect of codeine on gastric, small-bowel, and colonic transit time in healthy volunteers.


METHODS
Seventy-four healthy participants (43 women) were randomized in a double-blind, placebo-controlled manner to 1 of 4 groups: alvimopan 12 mg twice daily in the presence and absence of codeine sulfate 30 mg 4 times/day, or codeine or placebo alone. Gastric emptying, small-bowel, and colonic transit were measured by scintigraphy using a 99m-labeled technetium egg meal and 111-labeled indium charcoal delivered to the proximal colon via a delayed-release capsule. The primary end points for colonic transit were geometric center of the colonic counts at 24 hours and time for 50% ascending colon emptying. Analysis of covariance was used to assess the significance of the primary and secondary end points.


RESULTS
Codeine delayed gastric, small-bowel, proximal, and overall colonic transit (P < .05). Alvimopan reversed codeine's effect on small bowel and colon (ascending colon and overall colonic transit). Alvimopan also accelerated overall colonic transit compared with placebo. Thus, the mean colonic geometric center at 24 hours was 2.33 with placebo/placebo, 3.25 with alvimopan/placebo (P < .05), 1.5 with placebo/codeine (P < .05), and 2.63 with alvimopan/codeine. Alvimopan did not reverse codeine's delay of gastric emptying.


CONCLUSIONS
Alvimopan reverses codeine's inhibitory effect on small-bowel and colon transit and has potential for treatment of opiate bowel dysfunction. Alvimopan alone accelerates colonic transit, suggesting that mu-opiate mechanisms participate in the physiologic control of colonic transit.
Gonenne
Jonathan
J
Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Camilleri
Michael
M
Ferber
Irene
I
Burton
Duane
D
Baxter
Kari
K
Keyashian
Kian
K
Foss
Joseph
J
Wallin
Bruce
B
Du
Wei
W
Zinsmeister
Alan R
AR
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D003061:Codeine / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011877:Radionuclide Imaging
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; C419502:alvimopan; D003061:Codeine