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BJA Advance Access published online on January 16, 2006
British Journal of Anaesthesia, doi:10.1093/bja/aei316
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted December 8, 2005

Clinical Investigation

Pharmacokinetics of S(+) ketamine derived from target controlled infusion

M. White 1 *, P. de Graaff 1, B. Renshof 1, E. van Kan 2, and M. Dzoljic 1

1 Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands
2 Department of Clinical Pharmacy, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands

* To whom correspondence should be addressed.
M. White, E-mail: m.white{at}amc.uva.nl


  Abstract

Background. A computer controlled infusion device for S(+) ketamine was used in combination with a Diprifusor® device to provide anaesthesia for 20 ASA I or II patients undergoing elective colonoscopy. The aim of the study was to assess the performance of the pharmacokinetic model for S(+) ketamine used in the delivery algorithm of the device.

Results. It was observed that during the first 30 min of infusion there was systematic underprediction by the delivery system of the measured levels of S(+) ketamine. New pharmacokinetic constants were derived from the observed data which provided, on pharmacokinetic simulation, improved prediction of the measured values of S(+) ketamine. Prospective application of this modified model for S(+) ketamine in a further nine study patients was performed and the pharmacokinetic performance of the model was reassessed. The data from all 29 patients was subsequently used to calculate the population distribution of S(+) ketamine clearance. The distribution was found to be normal only in the logarithmic domain. In the normal domain the mode of S(+) ketamine clearance was found to be 35.8 ml kg-1 min-1 with 5 and 95% confidence limits of, respectively, 11.5 and 111.1 ml kg-1 min-1.

Conclusion. It was necessary to modify the original published pharmacokinetic parameters incorporated into the S(+) ketamine delivery system in order to simulate improved PK performance during short procedures (<1 h duration) where propofol was concurrently administered. This improved performance was confirmed in a further prospective study.

Keywords: anaesthetics i.v., ketamine; anaesthetics i.v., propofol; anaesthetics i.v., target controlled infusion; pharmacokinetics.
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