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Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus.

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.

SUBMITTER: Viscusi ER

PROVIDER: S-EPMC4937649 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus.

Viscusi Eugene R ER Rathmell James P JP Fichera Alessandro A Binderow Sander R SR Israel Robert J RJ Galasso Frank L FL Penenberg Darryl D Gan Tong J TJ

Journal of drug assessment 20130827 1

<h4>Objective</h4>This phase 2 study evaluated the safety and activity of intravenous methylnaltrexone on the duration of postoperative ileus in patients undergoing segmental colectomy.<h4>Methods</h4>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 methyln ...[more]

PMID: 27536446

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Project description:N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use of intravenous DMT, data are lacking on its clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial in 27 healthy participants to test different intravenous DMT administration regimens: placebo, low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus + low infusion (15 mg + 0.6 mg/min), and high bolus + high infusion (25 mg + 1 mg/min). Study sessions lasted for 5 h and were separated by at least 1 week. Participant's lifetime use of psychedelics was ≤20 times. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics of DMT, and plasma levels of brain-derived neurotropic factor (BDNF) and oxytocin. Low (15 mg) and high (25 mg) DMT bolus doses rapidly induced very intense psychedelic effects that peaked within 2 min. DMT infusions (0.6 or 1 mg/min) without a bolus induced slowly increasing and dose-dependent psychedelic effects that reached plateaus after 30 min. Both bolus doses produced more negative subjective effects and anxiety than infusions. After stopping the infusion, all drug effects rapidly decreased and completely subsided within 15 min, consistent with a short early plasma elimination half-life (t1/2α) of 5.0-5.8 min, followed by longer late elimination (t1/2β = 14-16 min) after 15-20 min. Subjective effects of DMT were stable from 30 to 90 min, despite further increasing plasma concentrations, thus indicating acute tolerance to continuous DMT administration. Intravenous DMT, particularly when administered as an infusion, is a promising tool for the controlled induction of a psychedelic state that can be tailored to the specific needs of patients and therapeutic sessions.Trial registration: ClinicalTrials.gov identifier: NCT04353024.

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Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus.

Publications

Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus.

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