Pharmacokinetic and pharmacodynamic characterization of remimazolam in older Japanese adults who underwent general anesthesia at early stage of infusion.

The pharmacokinetic and pharmacodynamic characteristics of remimazolam (RMZ), a novel ultrashort-acting anesthetic, administration alone in clinical practice remain poorly understood. Therefore, we aimed to evaluate the relationship between patient characteristics and the pharmacokinetics and pharmacodynamics of RMZ in older Japanese adults who underwent general anesthesia at the early stage of infusion. Plasma samples were collected from 20 patients (median age: 71.7 years; range: 42.2-88.6 years) who were intravenously administered RMZ without other anesthetics such as remifentanil or fentanyl. The pharmacokinetic profiles of RMZ and its metabolite (CNS7054) were described using three- and two-compartment models with a transit compartment, respectively. The bispectral index was selected as a clinical measure of sedation. The pharmacokinetic-pharmacodynamic profile of RMZ was described using a maximum inhibitory model with an effect compartment. The population pharmacokinetic and pharmacodynamic parameters of RMZ were obtained using the nonlinear mixed-effects modeling program. RMZ clearance (CL) was increased nonlinearly with increasing body weight (BW), and the population mean CL for a typical patient (BW, 60.4 kg) was 1.38 L/min. No patient characteristics affected CNS7054 pharmacokinetics. The population mean of the half-maximal inhibitory RMZ concentration decreased nonlinearly with increasing age or BW. However, these characteristics did not meet the criteria for pharmacokinetic and pharmacodynamic covariates. Our results suggest that BW is an intrinsic factor affecting RMZ pharmacokinetics in Japanese patients under general anesthesia in the early stages of infusion; however, no patient characteristics affected RMZ pharmacodynamics.