 |
|
Methylnaltrexone for Reversal of Constipation Due to Chronic Methadone Use
A Randomized Controlled Trial
Chun-Su Yuan, MD, PhD;
Joseph F. Foss, MD;
Michael O'Connor, MD;
Joachim Osinski, MD;
Theodore Karrison, PhD;
Jonathan Moss, MD PhD;
Michael F. Roizen, MD
JAMA. 2000;283:367-372.
Context Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient.
Objective To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation.
Design Double-blind, randomized, placebo-controlled trial conducted between May 1997 and December 1998.
Setting Clinical research center of a university hospital.
Participants Twenty-two subjects (9 men and 13 women; mean [SD] age, 43.2 [5.5] years) enrolled in a methadone maintenance program and having methadone-induced constipation.
Main Outcome Measures Laxation response, oral-cecal transit time, and central opioid withdrawal symptoms were compared between the 2 groups.
Results The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous methylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for subjects in the methylnaltrexone and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in the methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly greater than the average change in the placebo group (-1.4 [12.0] minutes; P<.001). No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study.
Conclusions Our data demonstrate that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid-induced constipation.
Author Affiliations: Committee on Clinical Pharmacology (Drs Yuan, Foss, and Roizen) and Departments of Anesthesia and Critical Care (Drs Yuan, Foss, O'Connor, Moss, Roizen, and Mr Osinski) and Health Studies (Dr Karrison), Pritzker School of Medicine, University of Chicago, Chicago, Ill.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
January 19, 2000
JAMA. 2000;283(3):411-412.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Recent Advances in Pharmacotherapy
Kemp and Brown
Journal of Pharmacy Practice 2009;22:446-466.
ABSTRACT
Methylnaltrexone, a Peripherally Acting Opioid Receptor Antagonist, Enhances Tumoricidal Effects of 5-FU on Human Carcinoma Cells
WANG et al.
Anticancer Res 2009;29:2927-2932.
ABSTRACT
| FULL TEXT
Peripherally Acting Mu-Opioid Receptor Antagonists and Postoperative Ileus: Mechanisms of Action and Clinical Applicability
Viscusi et al.
Anesth. Analg. 2009;108:1811-1822.
ABSTRACT
| FULL TEXT
Development of Peripheral Opioid Antagonists: New Insights Into Opioid Effects
Moss and Rosow
Mayo Clin Proc. 2008;83:1116-1130.
ABSTRACT
| FULL TEXT
Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor-induced angiogenesis
Singleton et al.
Molecular Cancer Therapeutics 2008;7:1669-1679.
ABSTRACT
| FULL TEXT
Methylnaltrexone for Opioid-Induced Constipation in Advanced Illness
Thomas et al.
NEJM 2008;358:2332-2343.
ABSTRACT
| FULL TEXT
Emerging pharmacologic options for treating postoperative ileus
Kraft
Am J Health Syst Pharm 2007;64:S13-S20.
ABSTRACT
| FULL TEXT
Attenuation of Vascular Permeability by Methylnaltrexone: Role of mOP-R and S1P3 Transactivation
Singleton et al.
Am. J. Respir. Cell Mol. Bio. 2007;37:222-231.
ABSTRACT
| FULL TEXT
Methylnaltrexone Mechanisms of Action and Effects on Opioid Bowel Dysfunction and Other Opioid Adverse Effects
Yuan
The Annals of Pharmacotherapy 2007;41:984-993.
ABSTRACT
| FULL TEXT
Tolerability, Gut Effects, and Pharmacokinetics of Methylnaltrexone Following Repeated Intravenous Administration in Humans
Yuan et al.
J Clin Pharmacol 2005;45:538-546.
ABSTRACT
| FULL TEXT
Are Peripheral Opioid Antagonists the Solution to Opioid Side Effects?
Bates et al.
Anesth. Analg. 2004;98:116-122.
ABSTRACT
| FULL TEXT
Methylnaltrexone Antagonizes Opioid-Mediated Enhancement of HIV Infection of Human Blood Mononuclear Phagocytes
Ho et al.
J. Pharmacol. Exp. Ther. 2003;307:1158-1162.
ABSTRACT
| FULL TEXT
Acute Pain Management
Koo
Journal of Pharmacy Practice 2003;16:231-248.
ABSTRACT
Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors
Moss et al.
NEJM 2002;346:455-455.
FULL TEXT
Effects of Subcutaneous Methylnaltrexone on Morphine-Induced Peripherally Mediated Side Effects: A Double-Blind Randomized Placebo-Controlled Trial
Yuan et al.
J. Pharmacol. Exp. Ther. 2002;300:118-123.
ABSTRACT
| FULL TEXT
Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors
Taguchi et al.
NEJM 2001;345:935-940.
ABSTRACT
| FULL TEXT
Pharmacokinetic profile of epidurally administered methylnaltrexone, a novel peripheral opioid antagonist in a rabbit model
Murphy et al.
Br J Anaesth 2001;86:120-122.
ABSTRACT
| FULL TEXT
Oral Methylnaltrexone for Opioid-Induced Constipation
Yuan and Foss
JAMA 2000;284:1383-1384.
FULL TEXT
|
