• Tae Kyun Kim, Shinju Obara, Talmage D Egan, Charles F Minto, Luca La Colla, David R Drover, Jaap Vuyk, Martijn Mertens, and the Remifentanil Pharmacokinetics in Obesity Investigators.
• From the Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Busan, Korea (T.K.K.); Department of Anesthesiology, Fukushima Medical University School of Medicine, Fukushima, Japan (S.O.); and Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah (T.D.E.).
• Anesthesiology. 2017 Jun 1; 126 (6): 1019-1032.

BackgroundThe 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.MethodsNine 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.ResultsBody 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 bootstrap procedure showed satisfactory CIs on all of the model parameters.ConclusionsA 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.

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