Nd. Hawkes et al., Effect of an enteric-release formulation of naloxone on intestinal transitin volunteers taking codeine, ALIM PHARM, 15(5), 2001, pp. 625-630
Introduction: Constipation is a common side-effect of opioid therapy; in ad
dition to their analgesic effect, opioids reduce intestinal secretion and m
otility with an increase in whore-gut transit time. Naloxone, a specific op
ioid antagonist, reverses these effects but may also cause symptoms of opio
id withdrawal in patients on long-term therapy.
Aim: To use an enteric-release formulation, designed to produce a topical e
ffect in the gut, with minimum systemic effects.
Methods: Naloxone 10 mg b.d, and codeine 30 mg b.d. were used with identica
l placebo capsules in four sets of studies; 12 male volunteers were given t
he drugs alone and in combination, with a control study involving double pl
acebo, during each of four study periods. Whole-gut transit time was calcul
ated 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 def
ecate was reported by two volunteers on naloxone alone and by three on comb
ination therapy.
Conclusions: The results show that the naloxone formulation counteracts the
effect of codeine on intestinal transit, suggesting that it may have usefu
l clinical applications.