Target controlled infusion of rocuronium: analysis of effect data to select a pharmacokinetic model

We aimed to evaluate whether area under the curve (AUC) analysis of pharmacodynamic data can be used to compare pharmacokinetic models taken from the literature, during a target controlled infusion (TCI) of rocuronium.

Seventy-two patients scheduled for orthopaedic surgery received a TCI of rocuronium (Stanpump) based on one of four pharmacokinetic models: those described by Szenohradszky, Alvarez-Gomez, Wierda, and Cooper. The resulting theoretical plasma concentration versus time curve was calculated for all patients based on all four pharmacokinetic models. Predicted effect versus time curves were calculated following the pharmacokinetic-pharmacodynamic link model (Sheiner and colleagues). Neuromuscular block was evaluated acceleromyographically. The difference between the area under the observed effect (AUC(OE)) and predicted effect (AUC(PE)) versus time curves was used for comparison.

AUC(PE )differed significantly from AUC(OE) in the Szenohradszky and Alvarez-Gomez models, both with the reference link-pharmacodynamic data and with altered link-pharmacodynamic variables. AUC(PE )and AUC(OE) were comparable for the Wierda and Cooper models. The mean AUC(OE) was 25.1 (SD 11.9)% block x h. AUC(PE)-AUC(OE) was significantly larger in the Szenohradszky model when compared with all other pharmacokinetic models. This difference remained when link or pharmacodynamic variables were modified. The smallest AUC(PE)-AUC(OE) difference was found with the Wierda model.

It was possible to use AUC analysis for identification of the pharmacokinetic model that best predicted the pharmacodynamic characteristics of our patients.