Respiratory and antinociceptive effects of NOP-MOP agonist cebranopadol versus full opioid receptor agonist oxycodone: a comparison in healthy volunteers.

Summary

In a randomized, double-blind, partial-crossover study in healthy volunteers, cebranopadol produced potent analgesia with significantly less respiratory depression than oxycodone. Population PK/PD modeling showed markedly different respiratory C50 and greater analgesic potency for cebranopadol.

Key Findings

• At equianalgesia, cebranopadol caused approximately 25% less respiratory depression than oxycodone based on PK/PD analysis.
• Oxygen desaturations (~80%) occurred in 65% after oxycodone 60 mg vs 25% after cebranopadol 1000 µg.
• Cebranopadol exhibited higher analgesic potency and a markedly lower respiratory C50 than oxycodone.

Clinical Implications

Cebranopadol may offer equianalgesic benefit with less respiratory compromise than oxycodone, supporting clinical trials in perioperative and chronic pain patients and cautious exploration as an opioid-sparing alternative.

Limitations

• Healthy volunteer study with surrogate endpoints; not clinical pain populations
• Short 24-hour observation; long-term safety and efficacy not assessed

Future Directions

Conduct patient-centered RCTs comparing cebranopadol with standard opioids in perioperative and chronic pain, including respiratory safety in high-risk populations and opioid-sparing strategies.