J Neurogastroenterol Motil.  2018 Jan;24(1):119-127. 10.5056/jnm17058.

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350

• Poulsen JL
• Mark EB
• Brock C
• Frøkjær
• Krogh K
• Drewes AM

• KMID: 2417279
• DOI: http://doi.org/10.5056/jnm17058

Abstract

BACKGROUND/AIMS
Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350.
METHODS
In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency.
RESULTS
Total colorectal volume did not change after 5 days' treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P < 0.001). Neither regional GI transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035).
CONCLUSIONS
PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment.

Keyword

Constipation; Motility; Naloxone; Opioids; Oxycodone

MeSH Terms

Analgesics, Opioid
Constipation
Humans
Laxatives
Magnetic Resonance Imaging
Magnets
Male
Models, Theoretical
Naloxone
Narcotic Antagonists
Oxycodone*
Polyethylene Glycols*
Analgesics, Opioid
Laxatives
Naloxone
Narcotic Antagonists
Oxycodone
Polyethylene Glycols