Rocuronium pharmacodynamic models for published five pharmacokinetic models: age and sex are covariates in pharmacodynamic models
Equilibration rate constant is necessary to calculate effect-site concentration, which is useful to control drug effect. We developed pharmacodynamic models for published five compartmental pharmacokinetic models published by Wierda, Szenohradszky, Cooper, Alvarez-Gomez, and McCoy.
We used 3848 train-of-four ratios from 15 male and nine female patients (21–76 years; 44–93 kg body weight; 148–181 cm height; and 17.3–29.8 kg/m2 body mass index) as pharmacodynamic measures, which were collected at the start of 0.6 mg/kg rocuronium administration until the end of the surgery. Effect compartment was assumed to be connected to central compartment of the pharmacokinetic model with equilibration rate constant (ke0). Sigmoid Emax model was fitted to describe the relationship between train-of-four ratio and effect-site concentration. Age, sex, and body mass index were assessed as possible covariates of the following model parameters: ke0, effect-site concentration for half of maximum effect, and the steepness of the effect-site concentration versus effect relationship.
The duration of neuromuscular monitoring was 69 (37–129) [median (range)] min. All pharmacodynamic models included age and three included sex as significant covariates. Ke0 values ranged between 0.0820 and 0.247 depending on the pharmacokinetic model. The time-courses of the effect-site concentration were similar among the pharmacodynamic models for Wierda, Cooper, and Alvarez-Gomez pharmacokinetic models, which were lower than that for the Szenohradszky pharmacokinetic model.
Each pharmacodynamic model with the corresponding pharmacokinetic model can be described the time course of rocuronium effect appropriately. The required effect-site concentration of rocuronium for a pharmacodynamic effect was depending on the applied models.
KeywordsNeuromuscular blockade Rocuronium Pharmacodynamics
Kenichi Masui: designed and conducted the study, analyzed and interpreted the data, and drafted and revised the manuscript. Sayaka Ishigaki: interpreted the data, and revised the manuscript. Atsuko Tomita: interpreted the data, and revised the manuscript. Hiroshi Otake: interpreted the data, and revised the manuscript.
Compliance with ethical standards
Conflict of interest
Support for this study was solely provided by departmental and institutional funding of Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan. Kenichi Masui is an Editor of the Journal of Anesthesia, and an associate editorial board member of the British Journal of Anaesthesia.