Rocuronium pharmacodynamic models for published five pharmacokinetic models: age and sex are covariates in pharmacodynamic models

Abstract

Purpose

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.

Methods

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 (k_e0). Sigmoid E_max 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: k_e0, effect-site concentration for half of maximum effect, and the steepness of the effect-site concentration versus effect relationship.

Results

The duration of neuromuscular monitoring was 69 (37–129) [median (range)] min. All pharmacodynamic models included age and three included sex as significant covariates. K_e0 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.

Conclusion

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.

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