Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: Results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain

Pain

Volumn 137, Issue 2, 2008, Pages 428-440

  Webster, Lynn ^a   Jansen, Jan Peter ^b   Peppin, John ^c   Lasko, Ben ^d   Irving, Gordon ^e   Morlion, Bart ^f   Snidow, Jerry ^g   Pierce, Amy ^g   Mortensen, Eric ^g   Kleoudis, Christi ^g   Carter, Eric ^g  

^a Lifetree Clinical Research and Pain Clinic   (United States)

^b Schwerpunktpraxis für Schmerztherapie und Ambulante Anästhesie   (Germany)

^c The Pain Treatment Center of the Bluegrass   (United States)

^d Manna Research   (Canada)

^e SWEDISH MEDICAL CENTER   (United States)

^f UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^g GLAXOSMITHKLINE   (United States)

Author keywords

Alvimopan; Antagonist; Constipation; Gastrointestinal motility; Opioid; Randomized controlled trial

Indexed keywords

ALVIMOPAN; BISACODYL; CODEINE; FENTANYL; HYDROCODONE; HYDROMORPHONE; METHADONE; MORPHINE; MU OPIATE RECEPTOR ANTAGONIST; OXYCODONE; PLACEBO; TRAMADOL;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ADULT; ANALGESIA; APPETITE DISORDER; ARTICLE; BACKACHE; BLOATING; BODY WEIGHT; CHRONIC PAIN; CLINICAL TRIAL; COMPETITIVE INHIBITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG ANTAGONISM; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEMALE; FLATULENCE; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRACT FUNCTION; HEADACHE; HUMAN; HYPERHIDROSIS; INTESTINE FUNCTION; INTESTINE FUNCTION DISORDER; MAJOR CLINICAL STUDY; MALE; NAUSEA; OPIOID INDUCED BOWEL DYSFUNCTION; OPIOID NDUCED BOWEL DYSFUNCTION; PAINFUL DEFECATION; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; RHINORRHEA; RISK BENEFIT ANALYSIS; SIDE EFFECT; THERAPY EFFECT; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; VOMITING;

ADULT; ANALGESICS, OPIOID; COLIC; CONSTIPATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; ENTERIC NERVOUS SYSTEM; FEMALE; GASTROINTESTINAL MOTILITY; HUMANS; INTESTINES; MALE; MIDDLE AGED; NARCOTIC ANTAGONISTS; PAIN; PIPERIDINES; PLACEBOS; RECEPTORS, OPIOID, MU; RISK ASSESSMENT; TREATMENT OUTCOME;

EID: 45549109284     PISSN: 03043959     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pain.2007.11.008     Document Type: Article

References (33)

1. Allan L., Hays H., Jensen N.H., Le Polain de Waroux B., Bolt M., Donald R., et al. Randomized crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 322 (2001) 1154-1158
2. Azodo I.A., and Ehrenpreis E.D. Alvimopan. Curr Opin Investig Drugs 3 (2002) 1496-1501
3. Bates J.J., Foss J.F., and Murphy D.B. Are peripheral opioid antagonists the solution to opioid side effects?. Anesth Analg 98 (2004) 116-122
4. Camilleri M. Alvimopan, a selective peripherally acting μ-opioid antagonist. Neurogastroenterol Motil 17 (2005) 157-165
5. Culpepper-Morgan J.A., Inturrisi C.E., Portenoy R.K., Foley K., Houde R.W., Marsh F., et al. Treatment of opioid-induced constipation with oral naloxone: a pilot study. Clin Pharmacol Ther 52 (1992) 90-95
6. De Luca A., and Coupar I.M. Insights into opioid action in the intestinal tract. Pharmacol Ther 69 (1996) 103-115
7. Fallon M.T. Constipation in cancer patients: prevalence, pathogenesis, and cost-related issues. Eur J Pain 3 (1999) 3-7
8. Frank L., Kleinman L., Farup C., Taylor L., and Miner Jr. P. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol 34 (1999) 870-877
9. Friedman J.D., and Dello Buono F.A. Opioid antagonists in the treatment of opioid-induced constipation and pruritus. Ann Pharmacother 35 (2001) 85-91
10. Gutstein H.B., and Akil H. Opioid analgesics. In: Hardman J.G., Limbird L.E., and Gilman A.G. (Eds). Goodman and Gilman's The pharmacological basis of therapeutics (2001), McGraw-Hill Medical Publishing Division, New York, NY 569-619
11. Himmelsbach C.K. The morphine abstinence syndrome, its nature and treatment. Ann Int Med 15 (1941) 829-839
12. Holzer P. Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett 361 (2004) 192-195
13. Hommel G. A stagewise rejective multiple test procedure based on a modified Bonferroni test. Biometrika 75 (1988) 383-386
14. Kalso E., Edwards J.E., Moore R.A., and McQuay H.J. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 112 (2004) 372-380
15. Kurz A., and Sessler D.I. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 63 (2003) 649-671
16. Liberto J.G., Herschler J.A., Jaffe J.H., Norbeck J.H., and Carpenter R.L. Effects of ADL 8-2698, a peripherally restricted mu opioid antagonist, on gut motility in methadone and LAAM-dependent patients with opioid-induced constipation: a dose-ranging study. Drug Alcohol Depend 63 (2001) S91
17. Liu M., and Wittbrodt E. Low-dose oral naloxone reverses opioid-induced constipation and analgesia. J Pain Symptom Manage 23 (2002) 48-53
18. Marquis P., De La Loge C., Dubois D., McDermott A., and Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol 40 (2005) 540-551
19. McNicol E., Horowicz-Mehler N., Fisk R.A., Bennett K., Gialeli-Goudas M., Chew P.W., et al. Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review. J Pain 4 (2003) 231-256
20. Meissner W., Schmidt U., Hartmann M., Kath R., and Reinhart K. Oral naloxone reverses opioid-associated constipation. Pain 84 (2000) 105-109
21. Moore R.A., and McQuay H.J. Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Arthritis Res Ther 7 (2005) R1046-R1051
22. Palmer CS, Ingham M, Schmier J, Flood E, Gourlay G, Dodd SL. Utility assessments of opioid treatment for patients with chronic non-cancer pain. In: Presented at the 20th Annual Scientific meeting of the American Pain Society, Phoenix, AZ, April 19-22; 2001 [Abstract 790].
23. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg 182 (2001) 11S-18S
24. Paulson D.M., Kennedy D.T., Donovick R.A., Carpenter R.L., Cherubini M., Techner L., et al. Alvimopan: an oral, peripherally acting, μ-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction - a 21-day treatment-randomized clinical trial. J Pain 6 (2005) 184-192
25. Rauck RL, Southern JP, Carpenter RL. Use of alvimopan, a peripherally restricted mu-opioid antagonist to speed gastrointestinal transit in patients with opioid induced bowel dysfunction. In: Presented at the 10th World Congress on Pain, San Diego, CA, August 17-22; 2002 [Abstract 1669].
26. Schmidt W.K. Alvimopan (ADL 8-2698) is a novel peripheral opioid antagonist. Am J Surg 182 (2001) 27S-38S
27. Schug S.A., Zech D., and Grond S. Adverse effects of systemic opioid analgesics. Drug Safety 7 (1992) 200-213
28. Thorpe D.M. Management of opioid-induced constipation. Curr Pain Headache Rep 5 (2001) 237-240
29. Van Orden H. Constipation: an overview of treatment. J Pediatr Health Care 18 (2004) 320-322
30. Walsh T.D. Prevention of opioid side effects. J Pain Symptom Manage 5 (1990) 362-367
31. Wood J.D., and Galligan J.J. Function of opioids in the enteric nervous system. Neurogastroenterol Motil 16 (2004) 17-28
32. Yuan C.S., Wei G., Foss J.F., O'Connor M., Karrison T., and Osinski J. Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial. J Pharmacol Exp Ther 300 (2002) 118-123
33. Zimmerman D.M., Gidda J.S., Cantrell B.E., Schoepp D.D., Johnson B.G., and Leander J.D. Discovery of a potent, peripherally selective trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonist for the treatment of gastrointestinal motility disorders. J Med Chem 37 (1994) 2262-2265