{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:05:42Z","timestamp":1787162742710,"version":"build-2736575974"},"reference-count":64,"publisher":"American Veterinary Medical Association (AVMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Objective<\/jats:bold>\n                    \u2014To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Animals<\/jats:bold>\n                    \u20145 healthy adult horses.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Procedures<\/jats:bold>\n                    \u2014Horses were treated with MNTX (1 mg\/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg\/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg\/kg, IV, q 12 hours) and morphine (0.5 mg\/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    \u2014The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 \u00b1 21.8 mL\/kg, t\n                    <jats:sub>1\/2<\/jats:sub>\n                    of 47.04 \u00b1 11.65 minutes, and clearance of 11.43 \u00b1 1.06 mL\/min\/kg. Adverse effects were not observed at doses \u2264 1 mg\/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\n                    \u2014Because MNTX does not cross the blood-brain barrier, administration of the drug should not alter the analgesic effects of opioids and may attenuate the adverse gastrointestinal effects associated with use of opioids in horses.\n                  <\/jats:p>","DOI":"10.2460\/ajvr.67.6.998","type":"journal-article","created":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T15:57:37Z","timestamp":1149177457000},"page":"998-1004","source":"Crossref","is-referenced-by-count":38,"title":["Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine"],"prefix":"10.2460","volume":"67","author":[{"given":"Pedro","family":"Boscan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Van Hoogmoed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno H.","family":"Pypendop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Farver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack R.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Baillieres Clin Gastroenterol","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0950-3528(88)90024-3","article-title":"Action of opiates on gastrointestinal function","volume":"2","author":"Bueno","year":"1988"},{"key":"ref2","series-title":"Pharmacol Ther","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0163-7258(95)02053-5","article-title":"Insights into opioid action in the intestinal tract","volume":"69","author":"De Luca","year":"1996"},{"key":"ref3","series-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1067\/mcp.2000.105037","article-title":"Effects of enteric-coated methylnaltrexone in preventing opioid-induced delay in oralcecal transit time","volume":"67","author":"Yuan","year":"2000"},{"key":"ref4","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"992","DOI":"10.2460\/ajvr.67.6.992","article-title":"Evaluation of the effect of the opioid agonist morphine on gastrointestinal tract function in horses","volume":"67","author":"Boscan","year":"2006"},{"key":"ref5","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1136\/vr.155.11.321","article-title":"Retrospective study of the risk factors and prevalence of colic in horses after orthopaedic surgery","volume":"155","author":"Senior","year":"2004"},{"key":"ref6","series-title":"Minerva Anestesiol","first-page":"162","article-title":"Use of selective opiate receptor inhibitors to prevent postoperative ileus","volume":"68","author":"Akca","year":"2002"},{"key":"ref7","series-title":"J Pain Symptom Manage","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0885-3924(02)00424-4","article-title":"Opioid antagonists: a review of their role in palliative care, focusing on use in opioid-related constipation","volume":"24","author":"Choi","year":"2002"},{"key":"ref8","series-title":"Eur J Pharmacol","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/0014-2999(82)90026-7","article-title":"Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists","volume":"78","author":"Russell","year":"1982"},{"key":"ref9","series-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/S0009-9236(96)90117-4","article-title":"Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized placebo-controlled trial","volume":"59","author":"Yuan","year":"1996"},{"issue":"(suppl 2)","key":"ref10","series-title":"Neurogastroenterol Motil","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/j.1743-3150.2004.00555.x","article-title":"Preclinical studies of opioids and opioid antagonists on gastrointestinal function","volume":"16","author":"Greenwood-Van Meerveld","year":"2004"},{"key":"ref11","series-title":"Am J Surg","doi-asserted-by":"publisher","first-page":"27S","DOI":"10.1016\/S0002-9610(01)00784-X","article-title":"Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist","volume":"182","author":"Schmidt","year":"2001"},{"key":"ref12","series-title":"Drugs","doi-asserted-by":"publisher","first-page":"649","DOI":"10.2165\/00003495-200363070-00003","article-title":"Opioid-induced bowel dysfunction: pathophysiology and potential new therapies","volume":"63","author":"Kurz","year":"2003"},{"key":"ref13","series-title":"Am J Surg","doi-asserted-by":"publisher","first-page":"19S","DOI":"10.1016\/S0002-9610(01)00783-8","article-title":"A review of the potential role of methylnaltrexone in opioid bowel dysfunction","volume":"182","author":"Foss","year":"2001"},{"key":"ref14","series-title":"Am J Physiol","first-page":"R1289","article-title":"Effects of abdominal or cardiopulmonary sympathetic afferents on upper cervical inspiratory neurons","volume":"278","author":"Yuan","year":"2000"},{"key":"ref15","series-title":"Equine Vet J","first-page":"325","article-title":"In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure","volume":"37","author":"van Hoogmoed","year":"2005"},{"key":"ref16","series-title":"Pharmacokinetics.","first-page":"45","article-title":"Multicompartment models","author":"Gibaldi","year":"1982"},{"key":"ref17","series-title":"J Pharmacokinet Biopharm","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/BF01117450","article-title":"Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations","volume":"6","author":"Yamaoka","year":"1978"},{"key":"ref18","series-title":"Equine Vet J","first-page":"622","article-title":"Tegaserod (HTF 919) stimulates gut motility in normal horses","volume":"36","author":"Lippold","year":"2004"},{"key":"ref19","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"464","DOI":"10.2460\/ajvr.2004.65.464","article-title":"Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine","volume":"65","author":"Teixeira Neto","year":"2004"},{"key":"ref20","series-title":"Am J Vet Res","first-page":"1762","article-title":"Cardiopulmonary and gastrointestinal motility effects of xylazine\/ketamine-induced anesthesia in horses previously treated with glycopyrrolate","volume":"57","author":"Singh","year":"1996"},{"key":"ref21","series-title":"Can J Vet Res","first-page":"99","article-title":"Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses","volume":"61","author":"Singh","year":"1997"},{"key":"ref22","series-title":"Eur J Pharmacol","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0014-2999(95)00018-G","article-title":"Effects of methylnaltrexone on morphine-induced inhibition of contraction in isolated guinea-pig ileum and human intestine","volume":"276","author":"Yuan","year":"1995"},{"key":"ref23","series-title":"Pain","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/S0304-3959(99)00162-1","article-title":"Effects of intravenous methylnaltrexone on opioid-induced gut motility and transit time changes in subjects receiving chronic methadone therapy: a pilot study","volume":"83","author":"Yuan","year":"1999"},{"key":"ref24","series-title":"Am J Vet Res","first-page":"311","article-title":"Investigation into the use of narcotic antagonists in the treatment of a stereotypic behavior pattern (crib-biting) in the horse","volume":"48","author":"Dodman","year":"1987"},{"key":"ref25","series-title":"J Clin Pharmacol","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1177\/009127009703700105","article-title":"Safety and tolerance of methylnaltrexone in healthy humans: a randomized, placebo-controlled, intravenous, ascending-dose, pharmacokinetic study","volume":"37","author":"Foss","year":"1997"},{"key":"ref26","series-title":"Lancet Oncol","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S1470-2045(02)00706-4","article-title":"Methylnaltrexone reverses opioid-induced constipation","volume":"3","author":"Stephenson","year":"2002"},{"key":"ref27","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1056\/NEJMoa010564","article-title":"Selective postoperative inhibition of gastrointestinal opioid receptors","volume":"345","author":"Taguchi","year":"2001"},{"key":"ref28","series-title":"Ann Surg","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1097\/01.sla.0000141158.27977.66","article-title":"Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus","volume":"240","author":"Wolff","year":"2004"},{"key":"ref29","series-title":"Gastroenterology","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/0016-5085(88)90673-7","article-title":"Role of opiate receptors in the regulation of colonic transit","volume":"94","author":"Kaufman","year":"1988"},{"key":"ref30","series-title":"Anesth Analg","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1213\/00000539-199377020-00023","article-title":"Influence of inhaled anesthetics on the pharmacokinetics and pharmacodynamics of morphine","volume":"77","author":"Steffey","year":"1993"},{"key":"ref31","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"166","DOI":"10.2460\/ajvr.2003.64.166","article-title":"Interactions of morphine and isoflurane in horses","volume":"64","author":"Steffey","year":"2003"},{"key":"ref32","series-title":"J Pharm Pharmacol","first-page":"655","article-title":"Studies to determine whether there is tolerance or cross-tolerance to the antisecretory effect of morphine and clonidine in the rat intestine","volume":"43","author":"Margaritis","year":"1991"},{"key":"ref1","series-title":"Baillieres Clin Gastroenterol","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0950-3528(88)90024-3","article-title":"Action of opiates on gastrointestinal function","volume":"2","author":"Bueno","year":"1988"},{"key":"ref2","series-title":"Pharmacol Ther","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0163-7258(95)02053-5","article-title":"Insights into opioid action in the intestinal tract","volume":"69","author":"De Luca","year":"1996"},{"key":"ref3","series-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1067\/mcp.2000.105037","article-title":"Effects of enteric-coated methylnaltrexone in preventing opioid-induced delay in oralcecal transit time","volume":"67","author":"Yuan","year":"2000"},{"key":"ref4","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"992","DOI":"10.2460\/ajvr.67.6.992","article-title":"Evaluation of the effect of the opioid agonist morphine on gastrointestinal tract function in horses","volume":"67","author":"Boscan","year":"2006"},{"key":"ref5","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1136\/vr.155.11.321","article-title":"Retrospective study of the risk factors and prevalence of colic in horses after orthopaedic surgery","volume":"155","author":"Senior","year":"2004"},{"key":"ref6","series-title":"Minerva Anestesiol","first-page":"162","article-title":"Use of selective opiate receptor inhibitors to prevent postoperative ileus","volume":"68","author":"Akca","year":"2002"},{"key":"ref7","series-title":"J Pain Symptom Manage","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0885-3924(02)00424-4","article-title":"Opioid antagonists: a review of their role in palliative care, focusing on use in opioid-related constipation","volume":"24","author":"Choi","year":"2002"},{"key":"ref8","series-title":"Eur J Pharmacol","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/0014-2999(82)90026-7","article-title":"Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists","volume":"78","author":"Russell","year":"1982"},{"key":"ref9","series-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/S0009-9236(96)90117-4","article-title":"Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized placebo-controlled trial","volume":"59","author":"Yuan","year":"1996"},{"issue":"(suppl 2)","key":"ref10","series-title":"Neurogastroenterol Motil","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/j.1743-3150.2004.00555.x","article-title":"Preclinical studies of opioids and opioid antagonists on gastrointestinal function","volume":"16","author":"Greenwood-Van Meerveld","year":"2004"},{"key":"ref11","series-title":"Am J Surg","doi-asserted-by":"publisher","first-page":"27S","DOI":"10.1016\/S0002-9610(01)00784-X","article-title":"Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist","volume":"182","author":"Schmidt","year":"2001"},{"key":"ref12","series-title":"Drugs","doi-asserted-by":"publisher","first-page":"649","DOI":"10.2165\/00003495-200363070-00003","article-title":"Opioid-induced bowel dysfunction: pathophysiology and potential new therapies","volume":"63","author":"Kurz","year":"2003"},{"key":"ref13","series-title":"Am J Surg","doi-asserted-by":"publisher","first-page":"19S","DOI":"10.1016\/S0002-9610(01)00783-8","article-title":"A review of the potential role of methylnaltrexone in opioid bowel dysfunction","volume":"182","author":"Foss","year":"2001"},{"key":"ref14","series-title":"Am J Physiol","first-page":"R1289","article-title":"Effects of abdominal or cardiopulmonary sympathetic afferents on upper cervical inspiratory neurons","volume":"278","author":"Yuan","year":"2000"},{"key":"ref15","series-title":"Equine Vet J","first-page":"325","article-title":"In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure","volume":"37","author":"van Hoogmoed","year":"2005"},{"key":"ref16","series-title":"Pharmacokinetics.","first-page":"45","article-title":"Multicompartment models","author":"Gibaldi","year":"1982"},{"key":"ref17","series-title":"J Pharmacokinet Biopharm","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/BF01117450","article-title":"Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations","volume":"6","author":"Yamaoka","year":"1978"},{"key":"ref18","series-title":"Equine Vet J","first-page":"622","article-title":"Tegaserod (HTF 919) stimulates gut motility in normal horses","volume":"36","author":"Lippold","year":"2004"},{"key":"ref19","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"464","DOI":"10.2460\/ajvr.2004.65.464","article-title":"Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine","volume":"65","author":"Teixeira Neto","year":"2004"},{"key":"ref20","series-title":"Am J Vet Res","first-page":"1762","article-title":"Cardiopulmonary and gastrointestinal motility effects of xylazine\/ketamine-induced anesthesia in horses previously treated with glycopyrrolate","volume":"57","author":"Singh","year":"1996"},{"key":"ref21","series-title":"Can J Vet Res","first-page":"99","article-title":"Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses","volume":"61","author":"Singh","year":"1997"},{"key":"ref22","series-title":"Eur J Pharmacol","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0014-2999(95)00018-G","article-title":"Effects of methylnaltrexone on morphine-induced inhibition of contraction in isolated guinea-pig ileum and human intestine","volume":"276","author":"Yuan","year":"1995"},{"key":"ref23","series-title":"Pain","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/S0304-3959(99)00162-1","article-title":"Effects of intravenous methylnaltrexone on opioid-induced gut motility and transit time changes in subjects receiving chronic methadone therapy: a pilot study","volume":"83","author":"Yuan","year":"1999"},{"key":"ref24","series-title":"Am J Vet Res","first-page":"311","article-title":"Investigation into the use of narcotic antagonists in the treatment of a stereotypic behavior pattern (crib-biting) in the horse","volume":"48","author":"Dodman","year":"1987"},{"key":"ref25","series-title":"J Clin Pharmacol","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1177\/009127009703700105","article-title":"Safety and tolerance of methylnaltrexone in healthy humans: a randomized, placebo-controlled, intravenous, ascending-dose, pharmacokinetic study","volume":"37","author":"Foss","year":"1997"},{"key":"ref26","series-title":"Lancet Oncol","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S1470-2045(02)00706-4","article-title":"Methylnaltrexone reverses opioid-induced constipation","volume":"3","author":"Stephenson","year":"2002"},{"key":"ref27","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1056\/NEJMoa010564","article-title":"Selective postoperative inhibition of gastrointestinal opioid receptors","volume":"345","author":"Taguchi","year":"2001"},{"key":"ref28","series-title":"Ann Surg","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1097\/01.sla.0000141158.27977.66","article-title":"Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus","volume":"240","author":"Wolff","year":"2004"},{"key":"ref29","series-title":"Gastroenterology","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/0016-5085(88)90673-7","article-title":"Role of opiate receptors in the regulation of colonic transit","volume":"94","author":"Kaufman","year":"1988"},{"key":"ref30","series-title":"Anesth Analg","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1213\/00000539-199377020-00023","article-title":"Influence of inhaled anesthetics on the pharmacokinetics and pharmacodynamics of morphine","volume":"77","author":"Steffey","year":"1993"},{"key":"ref31","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"166","DOI":"10.2460\/ajvr.2003.64.166","article-title":"Interactions of morphine and isoflurane in 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