Abstract
Objective
To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially
available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.
Study design
Prospective single-group interventional study.
Animals
A group of six healthy adult research ponies (four mares, two geldings).
Methods
Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg–1) and butorphanol (0.01 mg kg–1) for an unrelated study. Additional IV detomidine (0.004 mg kg–1) was administered 85 minutes later, followed by induction of anaesthesia using IV
diazepam (0.05 mg kg–1) and ketamine (2.2 mg kg–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken
after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg–1) with fenpipramide (0.0125 mg kg–1) was then administered IV. Selected cardiorespiratory variables were recorded every
10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events
were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics
of l-methadone were collected throughout anaesthesia at predetermined time points. Data
are shown as mean ± standard deviation or median and interquartile range (p < 0.05).
Results
Plasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination
phase which is best described with a two-compartment model. The terminal half-life
was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg–1 and plasma clearance 7.77 ± 1.98 mL minute–1 kg–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10
minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at
different time points after l-methadone administration.
Conclusions and clinical relevance
Administration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient
increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics
of l-methadone were similar to those reported for conscious horses administered racemic
methadone.
Keywords
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Article info
Publication history
Published online: December 08, 2020
Accepted:
April 24,
2020
Received:
April 28,
2019
Footnotes
☆Parts of this study have been presented at the Autumn Meeting of the Association of Veterinary Anaesthetists (AVA) in 2017 in Berlin, Germany.
Identification
Copyright
© 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
