Response Surface Modeling of Remimazolam and Sevoflurane

Condition(s) studied

Investigational drug(s) / intervention(s)

Remimazolam (Byfavo): Remimazolam will be administered at infusion rates ranging from 0 to 6 mg/kg/h using an infusion pump with pharmacokinetic simulation software.

Sevoflurane (Volatile Anesthetic): Sevoflurane will be administered by inhalation with targeted end-tidal concentrations between 0 and 2 vol%.

Study summary

This prospective randomized open-label study aims to investigate the pharmacodynamic interaction between remimazolam and sevoflurane during general anesthesia using response surface modeling. Although remimazolam has favorable hemodynamic stability compared with propofol, its hypnotic effect may be less predictable and poorly correlated with conventional sedation monitoring indices such as the bispectral index (BIS). In clinical practice, remimazolam and sevoflurane are often combined during induction and maintenance of anesthesia; however, the optimal interaction between these agents remains unclear.

This study will evaluate whether the interaction between remimazolam and sevoflurane is synergistic, additive, or infra-additive using two representative response surface interaction models: the Minto model and the Greco model. BIS values and predicted effect-site concentrations will be analyzed using NONMEM software.

Eligibility

Primary outcome measure(s)

• Interaction coefficient (α) between remimazolam and sevoflurane derived from the Minto response surface model — During anesthetic induction
  The interaction coefficient (α) describing the pharmacodynamic interaction between remimazolam effect-site concentration and end-tidal sevoflurane concentration will be estimated using the Minto response surface model based on BIS values collected during anesthetic induction.
• Interaction parameter between remimazolam and sevoflurane derived from the Greco response surface model — During anesthetic induction
  The pharmacodynamic interaction parameter describing the interaction between remimazolam effect-site concentration and end-tidal sevoflurane concentration will be estimated using the Greco response surface model based on BIS values collected during anesthetic induction.

Trial sites (1)

More Pusan National University Yangsan Hospital trials in South Korea