Tapentadol results in less deterioration of gastrointestinal function and symptoms than standard opioid therapy in healthy male volunteers.

Published on May 29, 2021in Neurogastroenterology and Motility2.946
· DOI :10.1111/NMO.14131
Esben Bolvig Mark9
Estimated H-index: 9
(AAU: Aalborg University),
Rasmus Bach Nedergaard2
Estimated H-index: 2
(AAU: Aalborg University)
+ 5 AuthorsAsbjørn Mohr Drewes78
Estimated H-index: 78
(AAU: Aalborg University)
BACKGROUND Tapentadol is a combined opioid agonist and norepinephrine reuptake inhibitor with fewer gastrointestinal side effects at equianalgesic doses compared with classical strong opioids. Previous studies on tapentadol have included multi-morbid patients in whom confounders exclude detailed assessment of the mechanistic effects and strict comparison with other opioids or placebo. This study aimed at investigating the effects of tapentadol and oxycodone on gastrointestinal motility and gastrointestinal side effects. METHODS 21 healthy males participated in a randomized, double-blind, placebo-controlled, crossover study. Tapentadol (50 mg twice daily), oxycodone (10 mg twice daily), or placebo tablets were administered for 14 days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires. KEY RESULTS During dosing with tapentadol, gastrointestinal side effects and motility parameters were on placebo level. Compared with tapentadol, oxycodone increased whole gut transit time by 17.9 hours (p = .015) and rectosigmoid transit time by 6.5 hours (p = .005). Compared with tapentadol, oxycodone also reduced long, fast antegrade colonic movements (p = .001). In comparison with placebo, oxycodone prolonged whole gut transit time by 31.6 hours, (p < .001). Moreover, less long, fast antegrade colonic movements (p = .002) were observed during oxycodone. For oxycodone only, slow colonic movements were associated with gastrointestinal side effects. CONCLUSIONS & INFERENCES In this mechanistic study, tapentadol caused significantly less colonic dysmotility and gastrointestinal side effects as compared with oxycodone in equianalgesic doses.
📖 Papers frequently viewed together
42 Citations
218 Citations
#1Esben Bolvig Mark (AAU: Aalborg University)H-Index: 9
#2Jens Brøndum Frøkjær (AAU: Aalborg University)H-Index: 32
Last. Asbjørn Mohr Drewes (AAU: Aalborg University)H-Index: 78
view all 5 authors...
OBJECTIVES Opioids are often used in treatment of severe pain, although many patients experience gastrointestinal side-effects like constipation. The aim of the current study was to investigate changes in colonic volume, as the result of both colonic motility and fluid transport, in healthy volunteers during opioid treatment with tapentadol as compared with oxycodone and placebo. METHODS In a randomized, double-blind, cross-over study, 21 healthy male volunteers were administered equianalgesic d...
#1Mette Winther Klinge (Aarhus University Hospital)H-Index: 4
#2Anne-Mette Haase (Aarhus University Hospital)H-Index: 8
Last. K Krogh (Steno Diabetes Center)H-Index: 2
view all 10 authors...
BACKGROUND Gastrointestinal (GI) symptoms are common in patients with diabetes mellitus (DM). The electromagnetic 3D-Transit system allows assessment of regional transit times and motility patterns throughout the GI tract. We aimed to compare GI transit times and detailed motility patterns of the colon in patients with DM and GI symptoms to those of healthy controls (HC). We further aimed to determine whether any abnormalities in motility were reversible by cholinergic stimulation. METHODS We co...
2 CitationsSource
#1Nicola de Bortoli (UniPi: University of Pisa)H-Index: 28
#2C. Prakash Gyawali (WashU: Washington University in St. Louis)H-Index: 29
Last. Edoardo Savarino (UNIPD: University of Padua)H-Index: 60
view all 13 authors...
BACKGROUND Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy. METHODS All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile ref...
4 CitationsSource
#1Anne Estrup Olesen (AAU: Aalborg University)H-Index: 21
#2Debbie Grønlund (AAU: Aalborg University)H-Index: 5
Last. Asbjørn Mohr Drewes (AAU: Aalborg University)H-Index: 78
view all 6 authors...
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.
6 CitationsSource
#1Priya Vijayvargiya (Mayo Clinic)H-Index: 16
#2Sina Jameie-Oskooei (Mayo Clinic)H-Index: 1
Last. Mohammad Hassan Murad (Mayo Clinic)H-Index: 100
view all 6 authors...
Background The relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial. Objective To assess association between gastric emptying and UGI Sx, independent of treatment. Design We performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullne...
50 CitationsSource
#1Esben Bolvig Mark (AAU: Aalborg University)H-Index: 9
#2Jakob Lykke Poulsen (AAU: Aalborg University)H-Index: 15
Last. Asbjørn Mohr Drewes (AAU: Aalborg University)H-Index: 78
view all 9 authors...
BACKGROUND: The Motilis 3D-Transit system tracks electromagnetic capsules as they traverse the gastrointestinal tract. The method is minimally invasive and ambulatory. Analysis has previously been limited to regional gut transit times, but new methods may allow detailed analysis of colonic motility. METHODS: Parameters of colonic motility were analyzed from 34 3D-Transit recordings performed in healthy volunteers (median age 28 years; 8 F). Characteristic propulsive velocities and lengths of mov...
17 CitationsSource
#1Adam D Farmer (QMUL: Queen Mary University of London)H-Index: 5
Last. Roberto De Giorgio (University of Ferrara)H-Index: 62
view all 6 authors...
Summary Opioids are potent analgesics used for the treatment of acute and chronic pain. Side-effects are common and among the most bothersome are those associated with opioid-induced bowel dysfunction, which includes opioid-induced constipation. In this Review, we provide a summary of the pathophysiology, diagnosis, and management of opioid-induced constipation, which can be defined as a change in baseline bowel habit or defecatory patterns following initiation, alteration, or increase of opioid...
22 CitationsSource
#1Jakob Lykke Poulsen (AAU: Aalborg University)H-Index: 15
#2Esben Bolvig Mark (AAU: Aalborg University)H-Index: 9
Last. Asbjørn Mohr Drewes (AAU: Aalborg University)H-Index: 78
view all 6 authors...
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 macr...
9 CitationsSource
#1Zengdong MengH-Index: 2
#2Jing Yu (SC: University of Southern California)H-Index: 1
Last. Rongzhong Huang (CQMU: Chongqing Medical University)H-Index: 5
view all 7 authors...
Aim of this study was to study the tolerability of opioid analgesia by performing a network meta-analysis (NMA) of randomized-controlled trials (RCTs) which investigated effectiveness of opioids for the management of chronic pain. Research articles reporting outcomes of RCT/s comparing 2 or more opioid analgesics for the management of chronic pain were obtained by database search. Bayesian NMAs were performed to combine direct comparisons between treatments with that of indirect simulated eviden...
7 CitationsSource
#1Richard RauckH-Index: 48
Last. James NorthH-Index: 10
view all 3 authors...
Chronic pain patients relying on chronic opioid therapy are often challenged with opioid-induced constipation (OIC), a difficult condition to treat that has a significant psychosocial impact on those who are affected (Bruner et al., J Pain Res, 8, 2015, 289). Unlike other side effects of opioids, OIC does not resolve over time during chronic opioid use, and treatments used for functional constipation often fail to provide adequate symptom relief (Nelson and Camilleri, Therap Adv Gastroenterol, 8...
13 CitationsSource
Cited By0