The impact of naloxegol treatment on gastrointestinal transit and colonic volume

Abstract

Abstract Aims Opioid treatment is associated with gastrointestinal (GI) side effects, known as opioid-induced bowel dysfunction (OIBD). Symptoms of OIBD are caused by opioid receptor activation in the enteric nervous system, which results in increased GI transit time and increased faecal volume in the colon. OIBD can be experimentally induced in healthy participants through oral oxycodone treatment. The aim of this study was to investigate whether administration of naloxegol, a peripherally restricted opioid antagonist, could reduce GI symptoms, GI transit time, and colorectal volume, using an experimental model of OIBD. Methods In a double blind crossover trial, twenty-five healthy males were randomly assigned to a six day treatment of oral oxycodone in combination with either oral naloxegol or placebo. At baseline and at day six, participants filled in the Patient Assessment of Constipation Symptom questionnaire, and colorectal volume was quantified with a magnetic resonance imaging method. Participants swallowed a small electromagnetic capsule, which allowed determination of total and segmental GI transit times, using the 3D-Transit system. Results In the established model of oxycodone induced OIBD, fewer GI symptoms were observed during naloxegol treatment, compared to placebo (P <0.01). Naloxegol decreased median total transit time by 27% (56 vs 71 h, P < 0.05) and decreased colorectal transit time by 33% (45 vs 59 h, P < 0.01), compared to placebo. No difference in colorectal volume was found between the two treatments. Conclusions In an experimental model of OIBD, GI symptoms and GI transit time were reduced during treatment with naloxegol, compared to placebo. However, naloxegol treatment did not reduce colorectal volume. These findings add information on the potential of naloxegol to be used in prevention and treatment of OIBD.