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. 2013 Aug 27;2(1):127-34.
doi: 10.3109/21556660.2013.838169. eCollection 2013.

Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus

Eugene R Viscusi  1 , James P Rathmell  2 , Alessandro Fichera  3 , Sander R Binderow  4 , Robert J Israel  5 , Frank L Galasso  5 , Darryl Penenberg  5 , Tong J Gan  6
Affiliations

Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus

Eugene R Viscusi et al. J Drug Assess. .

Abstract

Objective: This phase 2 study evaluated the safety and activity of intravenous methylnaltrexone on the duration of postoperative ileus in patients undergoing segmental colectomy.

Methods: Adults (aged 18 years or older) with American Society of Anesthesiologists physical status of I, II, or III who underwent segmental colectomy, including partial colectomy, sigmoidectomy, cecectomy, or anterior proctosigmoidectomy, via laparotomy with general anesthesia, received intravenous methylnaltrexone 0.30 mg/kg or placebo every 6 h beginning within 90 min after end of surgery. Treatment continued until 24 h after the patient tolerated solid foods, was discharged, or for 7 d maximum. Efficacy endpoints included measures of gastrointestinal recovery and time to discharge eligibility.

Results: A total of 65 patients (methylnaltrexone, n = 33; placebo, n = 32) were randomized. Mean time to first bowel movement was accelerated by 20 h (p = 0.038) and time to discharge eligibility was accelerated by 33 h (p = 0.049) with methylnaltrexone vs placebo. Opioid use was similar between groups until postoperative day 4, then fluctuated in the placebo group. Methylnaltrexone was generally well tolerated.

Conclusions: In this study, intravenous methylnaltrexone significantly decreased time to postoperative bowel recovery and eligibility for hospital discharge by ∼1 d, with an adverse event profile similar to placebo. These were two of several exploratory endpoints; not all efficacy endpoints showed a significant difference between methylnaltrexone and placebo. The efficacy results in this trial were not seen in two subsequent large-scale studies.

Keywords: Methylnaltrexone; Mu-opioid receptor antagonist; Opioids; Postoperative ileus.

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Figures

Figure 1.
Figure 1.
Chemical structures of morphine, the non-selective opioid antagonist naltrexone, and the selective opioid antagonist methylnaltrexone.
Figure 2.
Figure 2.
Patient disposition. *One ineligible patient was randomized to placebo but drug was not dispensed.
See this image and copyright information in PMC

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