Abstract
Objective
To investigate the pharmacokinetics and effects of methadone on behaviour and plasma
concentrations of cortisol and vasopressin in healthy dogs.
Study design
Randomized, cross-over, experimental trial.
Animals
Nine adult dogs (beagle and beagle cross breeds), four males and five females.
Methods
Methadone hydrochloride, 0.4 mg kg−1, was administered intravenously (IV) and subcutaneously (SC) with a crossover design.
Drug and hormone analyses in plasma were performed using Liquid Chromatography–Electrospray
Ionization–Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural
data were collected using a standardized protocol.
Results
After IV administration, the plasma concentration of methadone at 10 minutes was 82.1
± 9.2 ng mL−1 (mean ± SD), the terminal half-life was 3.9 ± 1.0 hours, the volume of distribution
9.2 ± 3.3 L kg−1 and plasma clearance 27.9 ± 7.6 mL minute−1 kg−1. After SC administration, time to maximal plasma concentration was 1.26 ± 1.04 hours
and maximal plasma concentration of methadone was 23.9 ± 14.4 ng mL−1, the terminal half-life was 10.7 ± 4.3 hours and bioavailability was 79 ± 22%. Concentrations
of both cortisol and vasopressin were increased for an hour following IV methadone.
The observed behavioural effects of methadone were decreased licking and swallowing
and an increase in whining after SC administration. The latter finding is notable
as it can be misinterpreted as pain when methadone is used as an analgesic.
Conclusion and clinical relevance
When methadone was administered by the SC route, the half-life was longer, but the
individual variation in plasma concentrations was greater compared with IV administration.
Increased frequency of whining occurred after administration of methadone and may
be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in
plasma may not be suitable for evaluating analgesia after methadone treatment.
Keywords
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Article info
Publication history
Accepted:
September 22,
2008
Received:
July 8,
2008
Identification
Copyright
© 2010 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Inc. All rights reserved.
