An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers.
Background
There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.


Methods
Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.


Results
All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).


Conclusions
In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.
['van der Schrier|R|R|', 'Jonkman|K|K|', 'van Velzen|M|M|', 'Olofsen|E|E|', 'Drewes|A M|AM|', 'Dahan|A|A|', 'Niesters|M|M|']
D000293:Adolescent D000328:Adult D000701:Analgesics, Opioid D018592:Cross-Over Studies D004311:Double-Blind Method D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D010098:Oxycodone D012016:Reference Values D012119:Respiration D000077432:Tapentadol D055815:Young Adult
opioids respiratory depression breathing hypercapnic ventilatory response opioid-induced respiratory depression