Perioperative Medicine  |   June 2017
Disposition of Remifentanil in Obesity: A New Pharmacokinetic Model Incorporating the Influence of Body Mass
Author Notes
  • 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.).
  • Submitted for publication December 8, 2015. Accepted for publication February 22, 2017.
    Submitted for publication December 8, 2015. Accepted for publication February 22, 2017.×
  • Corresponding articles on pages 993 and 1005.
    Corresponding articles on pages 993 and 1005.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • This work was last presented in preliminary, abstract form at the 91st Annual Scientific Meeting of the Korean Society of Anesthesiologists, Seoul, Korea, November 6 to 8, 2014.
    This work was last presented in preliminary, abstract form at the 91st Annual Scientific Meeting of the Korean Society of Anesthesiologists, Seoul, Korea, November 6 to 8, 2014.×
  • *Members of the Remifentanil Pharmacokinetics in Obesity Investigators are listed in the appendix.
    Members of the Remifentanil Pharmacokinetics in Obesity Investigators are listed in the appendix.×
  • Address correspondence to Dr. Egan: Department of Anesthesiology, SOM 3C444, 30 North 1900 East, Salt Lake City, Utah 84132. talmage.egan@hsc.utah.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Clinical Science / Endocrine and Metabolic Systems / Pain Medicine / Pharmacology
Perioperative Medicine   |   June 2017
Disposition of Remifentanil in Obesity: A New Pharmacokinetic Model Incorporating the Influence of Body Mass
Anesthesiology 6 2017, Vol.126, 1019-1032. doi:10.1097/ALN.0000000000001635
Anesthesiology 6 2017, Vol.126, 1019-1032. doi:10.1097/ALN.0000000000001635
Abstract

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 bootstrap 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.