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


OBJECTIVE
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 whole-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.
Hawkes
N D
ND
Department of Gastroenterology, University Hospital of Wales, Cardiff, UK.
Richardson
C
C
Evans
B K
BK
Rhodes
J
J
Lewis
S J
SJ
Thomas
G A
GA
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D003061:Codeine / Q000009:adverse effects*; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013608:Tablets, Enteric-Coated
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D013608:Tablets, Enteric-Coated; D009270:Naloxone; D003061:Codeine