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BJA Advance Access originally published online on June 10, 2009
British Journal of Anaesthesia 2009 103(1):26-37; doi:10.1093/bja/aep143
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© The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Pharmacokinetic models for propofol—defining and illuminating the devil in the detail

A. R. Absalom1,*, V. Mani2, T. De Smet3 and M. M. R. F. Struys4

1 University Division of Anaesthesia, Addenbrookes Hospital, Cambridge CB2 2QQ, UK
2 Royal Hospital for Sick Children, Dalnair Street, Glasgow G3 8SJ, UK
3 BVBA Demed, Hollebeek 145 B-9140, Temse, Belgium
4 Department of Anaesthesia, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

* Corresponding author. E-mail: ara30{at}wbic.cam.ac.uk

The recently introduced open-target-controlled infusion (TCI) systems can be programmed with any pharmacokinetic model, and allow either plasma- or effect-site targeting. With effect-site targeting the goal is to achieve a user-defined target effect-site concentration as rapidly as possible, by manipulating the plasma concentration around the target. Currently systems are pre-programmed with the Marsh and Schnider pharmacokinetic models for propofol. The former is an adapted version of the Gepts model, in which the rate constants are fixed, whereas compartment volumes and clearances are weight proportional. The Schnider model was developed during combined pharmacokinetic–pharmacodynamic modelling studies. It has fixed values for V1, V3, k13, and k31, adjusts V2, k12, and k21 for age, and adjusts k10 according to total weight, lean body mass (LBM), and height. In plasma targeting mode, the small, fixed V1 results in very small initial doses on starting the system or on increasing the target concentration in comparison with the Marsh model. The Schnider model should thus always be used in effect-site targeting mode, in which larger initial doses are administered, albeit still smaller than for the Marsh model. Users of the Schnider model should be aware that in the morbidly obese the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Finally, the two currently available open TCI systems implement different methods of effect-site targeting for the Schnider model, and in a small subset of patients the induction doses generated by the two methods can differ significantly.

Keywords: pharmacokinetics, propofol; pharmacokinetics, models; drug delivery, computerized; drug delivery, infusion; equipment, infusion systems


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E-letters:

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The devil is not only in the details.
Frank H Engbers, et al.
British Journal of Anaesthesia, 3 Nov 2009 [Full text]
Re: The devil is not only in the details.
Anthony R Absalom, et al.
British Journal of Anaesthesia, 25 Nov 2009 [Full text]

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