Respiratory and Antinociceptive Effects of Nociceptin Receptor–µ-Opioid Receptor Agonist Cebranopadol versus Full Opioid Receptor Agonist Oxycodone: A Comparison in Healthy Volunteers
Authors' conclusion
The primary endpoint showed separation between the respiratory effects of cebranopadol and oxycodone, with 25% less respiratory depression at equianalgesia, as observed in the pharmacokinetic/pharmacodynamic analysis.
Study context
- Population
- Healthy volunteers4 occasions each
- Participants
- 30 volunteers
- Comparison
- Oral cebranopadol or oxycodone vs placebo
- Placebon = 20reference
- Cebranopadol 600 µgn = 20
- Cebranopadol 800 µgn = 20
- Cebranopadol 1,000 µgn = 20
- Oxycodone 30 mgn = 20
- Oxycodone 60 mgn = 20
- Primary endpoint
- Mixed model analyses on respiratory endpoints
Methodological detailsdouble-blind, placebo-controlled, partial crossover
- Double-blind
- Placebo-controlled
- Partial crossover
Primary result
As reported in the abstract
Respiratory depression (ventilation at isohypercapnia)
- All cebranopadol and oxycodone doses vs Placebo: P < 0.0001
- Cebranopadol 600 µg vs Oxycodone 30 mg: P = 0.022
Further findings
Respiratory drug concentration causing 50% effect (PK/PD analysis) · exploratory population PK/PD analysis
Analgesia (electrical pain tolerance)
- Cebranopadol more potent than oxycodone in producing analgesia
Safety
Oxygen desaturations (to ≈80%)
- Oxygen desaturations (to ≈80%): all occurring when experimental respiratory or pain testing was not performed
Original publication
Respiratory and Antinociceptive Effects of Nociceptin Receptor–µ-Opioid Receptor Agonist Cebranopadol versus Full Opioid Receptor Agonist Oxycodone: A Comparison in Healthy Volunteers. Anesthesiology. Published 11 December 2025. doi:10.
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