The impact of naloxegol on anal sphincter function - Using a human experimental model of opioid-induced bowel dysfunction.
Eur J Pharm Sci
; 117: 187-192, 2018 May 30.
Article
in En
| MEDLINE
| ID: mdl-29432808
ABSTRACT
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 15â¯mg twice daily in combination with either oral naloxegol 25â¯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 -38.8â¯mmâ¯Hg; Pâ¯<â¯0.01). No differences in anal resting pressure and anal canal distensibility were found between treatments (all Pâ¯>â¯0.5). Naloxegol improved PAC-SYM symptoms (mean score over days; 2.6 vs 4.5, Pâ¯<â¯0.001) and improved stool consistency scores (mean score over days; 3.3 vs 2.9, Pâ¯<â¯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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anal Canal
/
Oxycodone
/
Polyethylene Glycols
/
Constipation
/
Analgesics, Opioid
/
Morphinans
/
Narcotic Antagonists
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Eur J Pharm Sci
Journal subject:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Year:
2018
Document type:
Article
Affiliation country:
Denmark