Neurocognitive Effect of Biased µ-Opioid Receptor Agonist Oliceridine, a Utility Function Analysis and Comparison with Morphine
Authors' conclusion
These data indicate that over the clinical concentration range, oliceridine is an analgesic with a favorable safety profile over morphine when considering analgesia and neurocognitive function.
Study context
- Population
- Male and female volunteers
- Participants
- 20 volunteers
- Comparison
- IV oliceridine vs morphine vs placebo
- Primary endpoint
- Utility function (probability of benefit [antinociception, cold pressor test] minus probability of neurocognitive harm [slowing of saccadic peak velocity, increased body sway])
Methodological detailsdouble-blind, placebo-controlled, partial block three-way crossover, population pharmacokinetic-pharmacodynamic analysis, utility function analysis
- Double-blind
- Placebo-controlled
- Partial block three-way crossover
- Population pharmacokinetic-pharmacodynamic analysis
- Utility function analysis
Primary result
As reported in the abstract
Utility function (benefit: antinociception; harm: saccadic peak velocity)
- Oliceridine utility positive across effect-site concentration 5 to 77 ng/ml (greater probability of benefit than harm)
- Morphine utility not significantly different from 0 from 0 to 100 ng/ml
- Similar observations for body sway
- Oliceridine vs Morphine: P < 0.01
Further findings
| Outcome | Oliceridine | Morphine | Estimate | P value |
|---|---|---|---|---|
| C50 (effect-site concentration causing 50% effect) | 13 ± 2 ng/ml | 23 ± 7 ng/ml | ||
| Antinociception C50 | 13 ± 2 | 23 ± 7 | ||
| Saccadic peak velocity C50 | 90 ± 14 | 54 ± 15 | ||
| Body sway C50 | 10 ± 2 | 5.6 ± 0.8 | ||
| Ratio of therapeutic indices, C50(benefit)/C50(harm) | ratio of therapeutic indices (saccadic peak velocity) 0.34 (95% CI 0.17–0.7) | P < 0.01 | ||
| Ratio of therapeutic indices, C50(benefit)/C50(harm) | ratio of therapeutic indices (body sway) 0.33 (95% CI 0.16–0.50) | P < 0.01 |
- C50 (effect-site concentration causing 50% effect): value = antinociception C50
Original publication
Neurocognitive Effect of Biased µ-Opioid Receptor Agonist Oliceridine, a Utility Function Analysis and Comparison with Morphine. Anesthesiology. Published 1 September 2023. doi:10.
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