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

@entity1 @entity4094 @entity2898
BACKGROUND: 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 @entity2898 . METHODS: Seventy-two @entity1 scheduled for orthopaedic surgery received a TCI of @entity2898 (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 @entity1 based on all four pharmacokinetic models. Predicted effect versus time curves were calculated following the pharmacokinetic-pharmacodynamic link model (Sheiner and colleagues). @entity4094 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. RESULTS: 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. CONCLUSION: It was possible to use AUC analysis for identification of the pharmacokinetic model that best predicted the pharmacodynamic characteristics of our @entity1 .
