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

        ( Jakob L Poulsen ),( Esben B Mark ),( Christina Brock ),( Jens B Frøkjær ),( Klaus Krogh ),( Asbjørn M Drewes ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.1

        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. (J Neurogastroenterol Motil 2018;24:119-127)

      • KCI등재

        Effects of Naloxegol on Gastrointestinal Transit and Colonic Fecal Volume in Healthy Participants Receiving Oxycodone

        Anne E Olesen,Debbie Grønlund,Esben B Mark,Klaus Krogh,Jens B Frøkjær,Asbjørn M Drewes 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.4

        Background/Aims Opioids cause gastrointestinal (GI) dysmotility, decrease gut secretion, and affect gut sphincters. Symptoms of opioid-induced bowel dysfunction may be alleviated by peripherally acting opioid antagonists like naloxegol, but detailed knowledge on GI effects of this drug is lacking. We hypothesized that naloxegol, compared to placebo, would reduce GI transit time and colonic fecal volume in opioid-treated healthy participants. Methods We conducted a randomized, double-blinded, single-center, 2-way cross-over study in 24 healthy males, randomized to a 6 day treatment period of oxycodone (15 mg twice a day) co-administered with either naloxegol (25 mg once a day) or matching placebo. Participants swallowed an electromagnetic capsule which determined GI transit times. Colonic fecal volume was quantified with magnetic resonance imaging both pre-treatment and post-treatment. Results Naloxegol reduced total GI transit time by 21% (56 hours vs 71 hours, P = 0.02) and colonic transit time by 23% (45 hours vs 59 hours, P < 0.01), compared to placebo. However, no difference in colonic fecal volume was found (818 mL vs 884 mL, P = 0.20). Conclusions Short-term administration of naloxegol in healthy participants reverses the retardation of total GI and colonic transit induced by oxycodone. This supports the use of naloxegol in the treatment of GI side effects to opioid treatment, and add knowledge to the current understanding of mechanisms behind peripherally-acting opioid antagonists.

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        Gastric Emptying Time and Volume of the Small Intestine as Objective Markers in Patients With Symptoms of Diabetic Enteropathy

        ( Mette W Klinge ),( Nanna Sutter ),( Esben B Mark ),( Anne-mette Haase ),( Per Borghammer ),( Vincent Schlageter ),( Sten Lund ),( Jesper Fleischer ),( Karoline Knudsen ),( Asbjørn M Drewes ),( Klaus 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.3

        Background/Aims Patients with diabetes mellitus (DM) often suffer from gastrointestinal (GI) symptoms, but these correlate poorly to established objective GI motility measures. Our aim is to perform a detailed evaluation of potential measures of gastric and small intestinal motility in patients with DM type 1 and severe GI symptoms. Methods Twenty patients with DM and 20 healthy controls (HCs) were included. GI motility was examined with a 3-dimensional-Transit capsule, while organ volumes were determined by CT scans. Results Patients with DM and HCs did not differ with regard to median gastric contraction frequency (DM: 3.0 contractions/minute [interquartile range {IQR}, 2.9-3.0]; HCs: 2.9 [IQR, 2.8-3.1]; P = 0.725), amplitude of gastric contractions (DM: 9 mm [IQR, 8-11]; HCs: 11 mm (IQR, 9-12); P = 0.151) or fasting volume of the stomach wall (DM: 149 ㎤ [IQR, 112-187]; HCs: 132 ㎤ [IQR, 107-154]; P = 0.121). Median gastric emptying time was prolonged in patients (DM: 3.3 hours [IQR, 2.6-4.6]; HCs: 2.4 hours [IQR, 1.8-2.7]; P = 0.002). No difference was found in small intestinal transit time (DM: 5 hours [IQR, 3.7-5.6]; HCs: 4.8 hours [IQR, 3.9-6.0]; P = 0.883). However, patients with DM had significantly larger volume of the small intestinal wall (DM: 623 ㎤ [IQR, 487-766]; HCs: 478 ㎤ [IQR, 393-589]; P = 0.003). Among patients, 13 (68%) had small intestinal wall volume and 9 (50%) had gastric emptying time above the upper 95% percentile of HCs. Conclusion In our study, gastric emptying time and volume of the small intestinal wall appeared to be the best objective measures in patients with DM type 1 and symptoms and gastroenteropathy. (J Neurogastroenterol Motil 2021;27:390-399)

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