Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine

Introduction: Constipation is a common side-effect of opioid therapy; in addition to their analgesic effect, opioids reduce intestinal secretion and motility with an increase in whore-gut transit time. Naloxone, a specific opioid antagonist, reverses these effects but may also cause symptoms of opioid withdrawal in patients on long-term therapy. Aim: To use an enteric-release formulation, designed to produce a topical effect in the gut, with minimum systemic effects. Methods: Naloxone 10 mg b.d, and codeine 30 mg b.d. were used with identical placebo capsules in four sets of studies; 12 male volunteers were given the drugs alone and in combination, with a control study involving double placebo, during each of four study periods. Whole-gut transit time was calculated and compared for each treatment period. Results: Naloxone, both alone and with codeine, significantly shortened the mean whore-gut transit time compared with the control period, respectively, from 53.1 to 42.1 h (P = 0.005) and to 40.7 h (P = 0.024). Urgency to defecate was reported by two volunteers on naloxone alone and by three on combination therapy. Conclusions: The results show that the naloxone formulation counteracts the effect of codeine on intestinal transit, suggesting that it may have useful clinical applications.