Skip to main content
. 2011 Jul 14;5:201–211. doi: 10.4137/CMO.S4867

Table 3.

Trials on humans.

Author Design n Intervention Results
Yuan 1996 Phase I/II, randomised, double-blind, crossover placebo-controlled 12 healthy volunteers

  1. Group: intravenous placebo,

  2. Group: placebo plus 0.05 mg/kg morphine

  3. Group: 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine.

 Morphine significantly increased oral-cecal transit time from 104.6 +/− 31.1 minutes (mean +/− SD) to 163.3 +/− 39.8 minutes (P < 0.01).
Methylnaltrexone prevented 97% of morphine-induced increase in oral-cecal transit time
Murphy 1997 Phase I/II, randomised, double-blind, crossover placebo-controlled 11 healthy volunteers

  1. Group: placebo (saline),

  2. Group: 0.09 mg/kg morphine

  3. Group: 0.09 mg/kg morphine plus 0.3 mg/kg methylnaltrexone

 Methylnaltrexone given concomitantly with morphine reverses almost completely the morphine-induced delay in gastric emptying
Yuan 1997 Phase II, non-randomised, single-blind dose-escalation 14 healthy volunteers Descending doses of oral Methylnaltrexone (from 19.2 mg/kg) with 6.4 mg/kg oral methylnaltrexone significantly attenuated the morphine-induced delay in oral-cecal transit time dose-dependent response was obtained.
Yuan 1997 Phase II, non-randomised, single-blind dose-escalation 14 healthy Volunteers Ascending doses of oral methylnaltrexone (0.64, 6.4, 19.2 mg/kg/KG) Safe and well tolerated up to maximum dose
Yuan 1997 Phase II, randomized, double-blind, placebo-controlled 14 healthy volunteers

  1. Group group single-blind oral placebo and intravenous placebo

  2. Group: oral placebo and intravenous morphine (0.05 mg/kg) or

  3. Group: oral methylnaltrexone (19.2 mg/kg) and intravenous morphine (0.05 mg/kg).

 Oral methylnaltrexone (19.2 mg/kg) completely prevented morphine-induced increase in oral-cecal transit time
Yuan 2000 Phase II, randomised, double-blind, placebo-controlled 22 methadone users

  1. Placebo; group

  2. 0.015–0.365 mg/kg Mntx all intravenously;

    Both groups tested on days 1 and 2

 Decrease from baseline in oral-cecal transit time (min, mean [SD]):
Group 1: 1.4 (12);
Group 2: 77.7 (37.2) (P < 0.01 vs. group 1);
no laxation with group 1 vs. laxation for all of group 2 (P < 0.01); no opioid withdrawal symptoms
Yuan 2000 Phase II, single-blind, dose ranging 12 methadone users Placebo followed next day with:
Group 1: 0.3 mg/kg Mntx
Group 2: 1.0 mg/kg Mntx
Group 3: 3.0 mg/kg Mntx all orally		 Time to bowel movement (h, mean [SD]):
Group 1 (results for 3 of 4 patients): 18.0 (8.7);
Group 2 (4 of 4 patients): 12.3 (8.7);
Group 3 (4 of 4 patients): 5.2 (4.5); Dose-response effect with drug, P = 0.04;
no adverse effects; no opioid withdrawal symptoms
Portenoy 2008 Phase III, double-blind, randomized, parallel-group, repeated dose, dose-ranging 33 patients in palliative care

  1. Group 1 mg sc Mntx

  2. Group 5 mg sc Mntx

  3. Group 12.5 mg sc Mntx

  4. Group 20 mg sc Mntx

 Laxation response in first four hours:

  1. 10% (n = 10)

  2. 43% (n = 7)

  3. 60% (n = 10)

  4. 33% (n = 6)
Thomas 2008 Phase III randomized, double-blind placebo-controlled, clinical trial 133 patients in palliative care

  1. Placebo

  2. Group 0.15 mg sc Mntx repeated day 3,5,7,9,11,13

 Laxation response in first four hours after first injection:

  1. 15%

  2. 48%


Laxation response in first four hours for each of the following injection:

  1. 9, 13, 7, 14, 10, 8%

  2. 46, 47, 38, 41, 37, 38%


More patients in MNTX group than with placebo had: improvement of stool consistency and bowel status
Reduction of difficulty of laxation and distress associated with constipation
Slatkin 2009 Phase III randomized, double-blind placebo-controlled, clinical trial 154 patients in palliative care

  1. Placebo

  2. Group: 0.15 mg sc Mntx

  3. Group: 0.3 mg sc Mntx

 Laxation response in first four hours:

  1. 14% (95% CI: 4%–23%)

  2. 62% (95% CI: 48%–76%)

  3. 58% (95% CI: 75%–71%)

Modified from Becker.12,13