Asbjørn Mohr Drewes

The impact of naloxegol on anal sphincter function - Using a human experimental model of opioid-induced bowel dysfunction

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DOI

  • Debbie Grønlund, Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  • ,
  • Jakob L Poulsen, Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  • ,
  • Klaus Krogh
  • Christina Brock
  • Donghua Liao
  • ,
  • Hans Gregersen, GIOME, Department of Surgery, Prince of Wales Hospital and Chinese University of Hong Kong, Shatin, Hong Kong.
  • ,
  • Asbjørn M Drewes
  • Anne E Olesen, Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Denmark. Electronic address: aneso@rn.dk.

BACKGROUND AND AIMS: Opioid treatment interferes with anal sphincter function and its regulation during defecation. This may result in straining, incomplete evacuation, and contribute to opioid-induced bowel dysfunction (OIBD). Employing an experimental model of oxycodone-induced OIBD, we hypothesized that co-administration of the peripherally acting μ-opioid antagonist naloxegol would improve anal sphincter function in comparison to placebo.

METHODS: In a double-blind randomized crossover trial, 24 healthy males were assigned to a six-day treatment of oral oxycodone 15 mg twice daily in combination with either oral naloxegol 25 mg once daily or placebo. At baseline and at day 6, anal resting pressure and the recto-anal inhibitory reflex (RAIR) were evaluated using manometry and rectal balloon distension. Furthermore, the functional lumen imaging probe was used to measure distensibility of the anal canal. Gastrointestinal symptoms were assessed with the Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire and the Bristol Stool Form Scale.

RESULTS: During oxycodone treatment, naloxegol improved RAIR-induced sphincter relaxation by 15% (-45.9 vs -38.8 mm Hg; P < 0.01). No differences in anal resting pressure and anal canal distensibility were found between treatments (all P > 0.5). Naloxegol improved PAC-SYM symptoms (mean score over days; 2.6 vs 4.5, P < 0.001) and improved stool consistency scores (mean score over days; 3.3 vs 2.9, P < 0.01).

CONCLUSIONS: In this experimental model of OIBD, naloxegol improved the RAIR and reduced gastrointestinal symptoms. Hence, in contrast to conventional laxatives, naloxegol may regulate opioid-induced anal sphincter dysfunction and facilitate the defecation process.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Pharmaceutical Sciences
Vol/bind117
Sider (fra-til)187-192
Antal sider6
ISSN0928-0987
DOI
StatusUdgivet - 30 maj 2018

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