Effects of Buprenorphine, Methylnaltrexone, and Their Combination on Gastrointestinal Transit in Healthy New Zealand White Rabbits.
Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these agents. Methylnaltrexone is a peripheral opioid antagonist that ameliorates opioid-induced gastrointestinal stasis in others species yet preserves the analgesic effects of buprenorphine. We evaluated whether methylnaltrexone reversed buprenorphine-induced gastrointestinal stasis in 8 healthy male New Zealand White rabbits. To measure gastrointestinal transit time, each rabbit received 20 barium-filled spheres through an orogastric tube. Rabbits then received 4 treatments in random order: buprenorphine (0.05 mg/kg SC), methylnaltrexone (1 mg/kg SC), both agents combined (B+M), or normal saline (control) every 12 h for 2 d. Fecal production was measured every 6 h, and water and food consumption, and body weight, were measured daily, for 5 d after each treatment. The time to appearance of the first sphere was significantly longer for buprenorphine group than for control and methylnaltrexone groups. Daily fecal output was lowest for buprenorphine and B+M, intermediate for control, and highest for methylnaltrexone. Water and food consumption were lower for groups buprenorphine and B+M than for control and methylnaltrexone. Body weight was not affected. In conclusion, treatment with buprenorphine 0.05 mg/kg BID for 2 d in healthy rabbits decreased food and water consumption, prolonged gastrointestinal transit time and decreased the fecal output. Coadministration of methylnaltrexone at 1 mg/kg did not alleviate these negative side effects.
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University. Ithaca, New York;, Email: martinflores@cornell.edu.
Manuel
M
Martin-Flores
Center for Animal Resources and Education, Cornell University. Ithaca, New York.
Bhupinder
B
Singh
College of Agriculture and Life Sciences, Cornell University. Ithaca, New York.
Courtney A
CA
Walsh
College of Agriculture and Life Sciences, Cornell University. Ithaca, New York.
Elizabeth P
EP
Brooks
College of Agriculture and Life Sciences, Cornell University. Ithaca, New York.
Lacic
L
Taylor
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University. Ithaca, New York.
Lisa M
LM
Mitchell
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D005243:Feces; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007756:Laboratory Animal Science; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D002047:Buprenorphine; D009271:Naltrexone