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

Abstract

Background/AimsOpioid-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. MethodsIn 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. ResultsTotal 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). ConclusionsPR 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.

MRI analysis of fecal volume and dryness: Validation study using an experimental oxycodone‐induced constipation model

“…All data analysis was performed using a semiautomatic volumetric segmentation platform (MatLab v. R2016a, MathWorks, Natick, MA) that has been used in several other studies. 18,20,23,24,26 In short, the observer outlines a coarse region of interest encapsulating the colon on each of the 35-40 abdominal coronal images where the colon is shown. The colon segmentation is divided in the four colonic segments: ascending colon and cecum, transverse colon, descending colon, and sigmoid colon and rectum.…”

“…All data analysis was performed using a semiautomatic volumetric segmentation platform (MatLab v. R2016a, MathWorks, Natick, MA) that has been used in several other studies . In short, the observer outlines a coarse region of interest encapsulating the colon on each of the 35–40 abdominal coronal images where the colon is shown.…”

“…13,14 Additionally, chyme heterogeneity in the ascending colon has been assessed with subjective observer scores, 13 and more objectively with imaging-based feature analysis. 15 Colonic segmental volumes can be quantified from T 2 -weighted MRI sequences, where the colon wall shows high contrast to surrounding fat tissue, [16][17][18][19] a method with high reliability between observers. 20 T 2 -weighted MRI has also been used to quantify the amount of free water pockets in the small bowel and colon after drinking water, due to the images' high signal strength corresponding to free water.…”

Normative values for region‐specific colonic and gastrointestinal transit times in 111 healthy volunteers using the 3D‐Transit electromagnet tracking system: Influence of age, gender, and body mass index

“…The study population consisted of 128 healthy volunteers who participated in 3D-Transit studies conducted at three research facilities in the United Kingdom and Denmark between March 2012 and November 2017 as follows: 73 from Aarhus, Denmark, as part of various clinical studies trialing the 3D-Transit system in healthy subjects and in patients with functional GI disorders; 13-16 30 from London, United Kingdom, as part of an observational study of colonic motility in constipation and aging; 22 25 from Aalborg, Denmark, as part of clinical studies assessing the impact of opioid treatment on regional GI transit 17,18 and in studies demonstrating the novel capabilities of the 3D-Transit system for the assessment of colonic motility. 19,20 Despite being pooled from separate studies, consistency of test protocols was maintained.…”

“…6,11 Such information can be obtained using the Motilis 3D-Transit system (Motilis Medica, SA, Lausanne, Switzerland), an emerging research tool that tracks the location and orientation of up to three ingestible electromagnetic capsules. [13][14][15][16] However, the novelty of the system lies in providing a detailed analysis of colonic motility in terms of regionspecific colonic transit times, 17,18 anatomical lengths of colonic segments, 19 and colonic motility patterns. [13][14][15][16] However, the novelty of the system lies in providing a detailed analysis of colonic motility in terms of regionspecific colonic transit times, 17,18 anatomical lengths of colonic segments, 19 and colonic motility patterns.…”