RT Journal
A1 Yuan C, Foss JF, O'Connor M, et al
T1 Methylnaltrexone for reversal of constipation due to chronic methadone use: A randomized controlled trial
JF JAMA
JO JAMA
YR 2000
FD January 19
VO 283
IS 3
SP 367
OP 372
DO 10.1001/jama.283.3.367
UL http://dx.doi.org/10.1001/jama.283.3.367
AB 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.