Equilibration rate constant, ke0, to determine effect-site concentration for the Masui remimazolam population pharmacokinetic model in general anesthesia patients.

Abstract

Effect-site concentration is widely used to determine drug dosage in anesthesia practice. To obtain effect-site concentration, a pharmacokinetic model with a corresponding equilibration rate constant between plasma and effect-site, ke0, is necessary. Remimazolam, a novel short-acting benzodiazepine, has been approved as anesthetic/sedative. Recently, a remimazolam pharmacokinetic model has been published using a large dataset including wide range of subject characteristics (416 males and 246 females, age 18-93years, total body weight 34-149kg, height 133-204cm, body mass index 14-61kgm-2, ASA physical status: I-IV, and Asian, White, American African, and 2 other races). This Masui model can be applicable to various patients, but a pharmacodynamic model including ke0 was not developed simultaneously. A previous article has indicated that the time to peak effect of drug after its bolus should be used to determine ke0 for a pharmacokinetic model without simultaneous development of corresponding pharmacodynamic model. The ke0 value can be calculated using numerical analysis but not algebraic solution. We provide the detail method of the numerical analysis and a tool to have ke0 value easily for the Masui remimazolam PK model. Additionally, we provide a multiple regression model to have ke0 value for the PK model.