Influence of Intravenous S-Ketamine on the Pharmacokinetics of Oral Morphine in Healthy Volunteers
Authors' conclusion
Intravenous S-ketamine inhibited the metabolism of oral morphine and delayed its absorption, resulting in a net reduction in the exposure to morphine during the first 1.5 hours.
Study context
- Population
- Healthy volunteers1 excluded (vomiting)
- Participants
- 12 volunteers
- Comparison
- IV S-ketamine vs placebo infusion during oral morphine
- Primary endpoint
- AUC 0-24 of morphine
Methodological detailspaired, double-blind, crossover
- Paired
- Double-blind
- Crossover
Primary result
As reported in the abstract
Morphine AUC 0-24
- AUC 0-24 similar between the 2 phases
Secondary outcomes
| Outcome | Estimate | P value |
|---|---|---|
| Morphine AUC 0-1.5 · 0-1.5 hoursReduced by 69% | ratio to control 0.31 (90% CI 0.15–0.65) | P = 0.0171 |
| M6G AUC 0-1.5 · 0-1.5 hoursReduced by 84% | ratio 0.16 (90% CI 0.07–0.37) | P = 0.0025 |
| M6G CmaxReduced by 43% | ratio 0.57 (90% CI 0.40–0.81) | P = 0.0155 |
Morphine tmax
- Morphine tmax increased by S-ketamine from 0.5 (range, 0.50-1.5) to 1.0 hour (range, 0.50-4.0)
- P = 0.010
M6G tmax
- M6G tmax increased by S-ketamine from 1.5 (range, 1.0-2.0) to 4.0 (range, 1.0-8.0) hours
- P = 0.0094
M3G AUC 0-1.5 · 0-1.5 hours
- M3G AUC 0-1.5 reduced by 85% (ratio 0.15; 90% CI, 0.05-0.43)
- P = 0.0083
M3G tmax
- M3G tmax increased from 1.0 (range, 0.5-1.5) to 4.0 hours (range, 1.0-8.0)
- P = 0.0063
M6G-to-morphine and M3G-to-morphine metabolic AUC ratios
- M6G-to-morphine ratio decreased by 47% (0.53; 90% CI, 0.39-0.71), 0 to 1.5 hours
- P = 0.0033
- M3G-to-morphine ratio decreased by 52% (0.48; 90% CI, 0.27-0.85), 0 to 1.5 hours
- P = 0.0043
- M6G-to-morphine ratio decreased by 15% (0.85; 90% CI, 0.78-0.92), 0 to 24 hours
- P = 0.0057
- M3G-to-morphine ratio decreased by 10% (0.90; 90% CI, 0.83-0.98), 0 to 24 hours
- P = 0.0468
Safety
- Vomiting · participant excluded from analyses — S-ketamine
- 1 events
Original publication
Influence of Intravenous S-Ketamine on the Pharmacokinetics of Oral Morphine in Healthy Volunteers. Anesth Analg. Published 21 September 2023. doi:10.
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