Abstract
Objective
To assess the differences in the pharmacokinetic profiles of S-ketamine, R-ketamine
and their metabolites, S-norketamine and R-norketamine, and to measure relevant physiologic
variables after intravenous administration of racemic (RS) ketamine or S-ketamine
alone in Beagle dogs sedated with medetomidine.
Study design
Experimental, blinded and randomized crossover study.
Animals
A total of six (three female and three male) adult Beagle dogs.
Methods
Medetomidine (450 μg m–2) was administered intramuscularly, followed by either S-ketamine (2 mg kg–1) or RS-ketamine (4 mg kg–1) 20 minutes later, both administered intravenously. Blood samples were collected
before medetomidine administration and at multiple time points 1–900 minutes following
the ketamine administration. Plasma samples were analysed using liquid chromatography–tandem
mass spectrometry. Heart rate, respiratory rate, noninvasive blood pressure, haemoglobin
saturation with oxygen and body temperature were measured at baseline, before ketamine
administration, and 1, 2, 5, 10, 15, 20 and 30 minutes after ketamine administration.
All cardiovascular variables, blood glucose, haemoglobin and lactate concentrations
were analysed using different linear mixed effects models; the significance was set
at p < 0.05.
Results
S-ketamine showed a two-compartment kinetic profile; no statistically significant
differences were observed between its concentrations or in the calculated pharmacokinetic
parameters following S- or RS-ketamine. When the racemic mixture was administered,
no differences were detected between R- and S-ketamine concentrations, but the area
under the curve (AUC) for R-norketamine was significantly lower than that for S-norketamine.
Clinically relevant physiologic variables did not show statistically significant differences
following the administration of the racemic mixture or of S-ketamine alone.
Conclusions and clinical relevance
This study performed in dogs showed that RS-ketamine and S-ketamine combined with
medetomidine showed enantioselective pharmacokinetics as S- and R-norketamine AUCs
were different, but S-ketamine levels were identical.
Keywords
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Article info
Publication history
Published online: November 06, 2019
Accepted:
August 19,
2019
Received in revised form:
August 8,
2019
Received:
June 12,
2018
Identification
Copyright
© 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
