Disposition of Remifentanil in Obesity A New Pharmacokinetic Model Incorporating the Influence of Body Mass

Background: The influence of obesity on the pharmacokinetic (PK) behavior of remifentanil is incompletely understood. The aim of the current investigation was to develop a new population PK model for remifentanil that would adequately characterize the influence of body weight (among other covariates, e.g., age) on the disposition of remifentanil in the general adult population. We hypothesized that age and various indices of body mass would be important covariates in the new model. Methods: Nine previously published data sets containing 4,455 blood concentration measurements from 229 subjects were merged. A new PK model was built using nonlinear mixed-effects modeling. Satisfactory model performance was assessed graphically and numerically; an internal, boot-strapping validation procedure was performed to determine the CIs of the model. Results: Body weight, fat-free body mass, and age (but not body mass index) exhibited significant covariate effects on certain three-compartment model parameters. Visual and numerical assessments of model performance were satisfactory. The boot-strap procedure showed satisfactory CIs on all of the model parameters. Conclusions: A new model estimated from a large, diverse data set provides the PK foundation for remifentanil dosing calculations in adult obese and elderly patients. It is suitable for use in target-controlled infusion systems and pharmacologic simulation.