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

• Published in: Journal of anesthesia Vol. 36; no. 6; pp. 757 - 762
• Main Authors: Masui, Kenichi, Hagihira, Satoshi
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.12.2022
• Subjects: Anesthesiology; Critical Care Medicine; Emergency Medicine; Intensive; Medicine; Medicine & Public Health; Pain Medicine; Special Article; Remimazolam; General anesthetic; Equilibration rate constant between plasma and effect-site; Effect-site concentration; Benzodiazepine
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-022-03099-8

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, k e0 , 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 18–93 years, total body weight 34–149 kg, height 133–204 cm, body mass index 14–61 kg m −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 k e0 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 k e0 for a pharmacokinetic model without simultaneous development of corresponding pharmacodynamic model. The k e0 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 k e0 value easily for the Masui remimazolam PK model. Additionally, we provide a multiple regression model to have k e0 value for the PK model.