A General Purpose Pharmacokinetic Model for Propofol

Eleveld, Douglas J. PhD*; Proost, Johannes H. PhD*; Cortínez, Luis I. MD; Absalom, Anthony R. MD*; Struys, Michel M. R. F. MD*‡

Anesthesia & Analgesia:
doi: 10.1213/ANE.0000000000000165
Anesthetic Pharmacology: Research Report

BACKGROUND: Pharmacokinetic (PK) models are used to predict drug concentrations for infusion regimens for intraoperative displays and to calculate infusion rates in target-controlled infusion systems. For propofol, the PK models available in the literature were mostly developed from particular patient groups or anesthetic techniques, and there is uncertainty of the accuracy of the models under differing patient and clinical conditions. Our goal was to determine a PK model with robust predictive performance for a wide range of patient groups and clinical conditions.

METHODS: We aggregated and analyzed 21 previously published propofol datasets containing data from young children, children, adults, elderly, and obese individuals. A 3-compartmental allometric model was estimated with NONMEM software using weight, age, sex, and patient status as covariates. A predictive performance metric focused on intraoperative conditions was devised and used along with the Akaike information criteria to guide model development.

RESULTS: The dataset contains 10,927 drug concentration observations from 660 individuals (age range 0.25–88 years; weight range 5.2–160 kg). The final model uses weight, age, sex, and patient versus healthy volunteer as covariates. Parameter estimates for a 35-year, 70-kg male patient were: 9.77, 29.0, 134 L, 1.53, 1.42, and 0.608 L/min for V1, V2, V3, CL, Q2, and Q3, respectively. Predictive performance is better than or similar to that of specialized models, even for the subpopulations on which those models were derived.

CONCLUSIONS: We have developed a single propofol PK model that performed well for a wide range of patient groups and clinical conditions. Further prospective evaluation of the model is needed.

In Brief

Published ahead of print April 10, 2014

Author Information

From the *Department of Anesthesiology, University Medical Center Groningen, University of Groningen, The Netherlands; Departmento de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; and Department of Anesthesia, Ghent University, Gent, Belgium.

Accepted for publication January 20, 2014.

Published ahead of print April 10, 2014

Funding: Departmental funding.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Douglas J. Eleveld, PhD, Department of Anesthesiology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. Address e-mail to d.j.eleveld@umcg.nl.

© 2014 International Anesthesia Research Society