Target-controlled Infusion of Remimazolam in Healthy Volunteers Shows Some Acute Tolerance
Authors' conclusion
In this study, it was shown that remimazolam-induced sedation is prone to tolerance development, which is potentially mediated by the CNS7054 concentration.
Study context
- Population
- Healthy volunteers receiving remimazolam alone by target-controlled infusion (TCI)first period data
- Participants
- 24 volunteers
- Comparison
- PK-PD models without vs with tolerance
- Outcome
- Relationship between remimazolam concentration, MOAAS score and BIS
Methodological detailsanalysis of a crossover dose-ranging clinical trial, three-period crossover, age and sex stratification, step-up and step-down TCI protocol, nonlinear mixed-effects modelling
- Analysis of a crossover dose-ranging clinical trial
- Three-period crossover
- Age and sex stratification
- Step-up and step-down TCI protocol
- Nonlinear mixed-effects modelling
Main finding
As reported in the abstract
Remimazolam–BIS–MOAAS relationship
- Tolerance significantly improved overall model fit for BIS and Modified Observer's Assessment of Alertness and Sedation (MOAAS) models
- P < 0.01
Further findings
| Outcome | Without tolerance | With tolerance |
|---|---|---|
| Predicted BIS after 30 min repeated bolus dosing (procedural sedation label regimen) | 54 (95% prediction interval 44–67) | 58 (95% prediction interval 48–70) |
| Predicted probability of MOAAS 2/3 after 30 min repeated bolus dosing | 2% (95% prediction interval 0–32%) | 8% (95% prediction interval 0–36%) |
| Predicted BIS after 60 min continuous infusion (GA label regimen) | 40 (95% prediction interval 33–50) | 50 (95% prediction interval 41–60) |
| Predicted probability of MOAAS 0 after 60 min continuous infusion | 87% (95% prediction interval 18–100%) | 59% (95% prediction interval 6–99%) |
Original publication
Target-controlled Infusion of Remimazolam in Healthy Volunteers Shows Some Acute Tolerance. Anesthesiology. Published 27 October 2023. doi:10.
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