Abstract
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. 21 healthy males participated in a randomized, double-blind, placebo-controlled, crossover study. Tapentadol (50mg twice daily), oxycodone (10mg twice daily), or placebo tablets were administered for 14days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires. 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. In this mechanistic study, tapentadol caused significantly less colonic dysmotility and gastrointestinal side effects as compared with oxycodone in equianalgesic doses.
Published Version
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