Abstract
Objective
To describe the pharmacokinetics of ketamine following a short intravenous (IV) infusion
to isoflurane-anesthetized rabbits.
Study design
Prospective experimental study.
Animals
A total of six adult healthy female New Zealand White rabbits.
Methods
Anesthesia was induced with isoflurane in oxygen. Following determination of isoflurane
minimum alveolar concentration (MAC), the isoflurane concentration was reduced to
0.75 MAC and ketamine hydrochloride (5 mg kg–1) was administered IV over 5 minutes. Blood samples were collected before and at 2,
5, 6, 7, 8, 9, 13, 17, 21, 35, 65, 125, 215 and 305 minutes after initiating the ketamine
infusion. Samples were processed immediately and the plasma separated and stored at
–80 °C until analyzed for ketamine and norketamine concentrations using liquid chromatography–mass
spectrometry. Compartment models were fitted to the concentration–time data for ketamine
and for ketamine plus norketamine using nonlinear mixed-effects (population) modeling.
Results
A three- and five-compartment model best fitted the plasma concentration–time data
for ketamine and for ketamine plus norketamine, respectively. For the ketamine only
model, the volume of distribution at steady state (Vss) was 3217 mL kg–1, metabolic clearance was 88 mL minute–1 kg–1 and the terminal half-life was 59 minutes. For the model including both ketamine
and norketamine, Vss were 3224 and 2073 mL kg–1, total metabolic clearance was 107 and 52 mL minute–1 kg–1 and terminal half-lives were 52 and 55 minutes for the parent drug and its metabolite,
respectively.
Conclusions and clinical relevance
This study characterized the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized
New Zealand White rabbits following short IV infusion. The results obtained herein
will be useful to determine ketamine infusion regimens in isoflurane-anesthetized
rabbits.
Keywords
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Article info
Publication history
Published online: February 25, 2020
Accepted:
February 12,
2020
Received:
August 29,
2019
Identification
Copyright
© 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
