[Article in Press]
Gittel, C; Schulz-Kornas, E; Sandbaumhüter, FA; Theurillat, R; Vervuert, I; Larenza Menzies, MP; Thormann, W; Braun, C
Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies.
Vet Anaesth Analg. 2020; S1467-2987(20)30254-3
Autor/innen der Vetmeduni Vienna:
Larenza Maria Paula
Universitätsklinik für Kleintiere, Klinische Abteilung für Anästhesiologie und perioperative Intensivmedizin
- To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.Prospective single-group interventional study.A group of six healthy adult research ponies (four mares, two geldings).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).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.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.Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.