Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain.

摘要: Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain opioid-induced bowel dysfunction (OBD), identify at least one treatment regimen that improves OBD. Following 2-week baseline period, 522 reporting or=25% accompanied by sensation incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent >or=30 mg oral morphine/day were randomized alvimopan 0.5mg twice daily (BID), 1mg once (QD), BID, placebo for 6 weeks. Compared placebo, there statistically clinically significant increase mean weekly SBM frequency over initial 3 weeks (primary endpoint) BID (+1.71 SBMs/week), QD (+1.64) (+2.52); P<0.001 all comparisons. Increased additional effects, including improvements symptoms such as stool consistency, abdominal bloating/discomfort, decreased appetite, sustained The most frequently reported adverse events pain, nausea, diarrhea, occurring more higher dosage groups. demonstrated best benefit-to-risk profile managing OBD this study population, side effect similar placebo. There no evidence opioid antagonism. Competitive peripheral antagonism opioids can restore GI function relieve without compromising analgesia.