% pubman genre = article
@article{item_3278032,
title = {{Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies}},
author = {Gittel, Claudia and Schulz-Kornas, Ellen and Sandbaumh{\"u}ter, Friederike A. and Theurillat, Regula and Vervuert, Ingrid and Menzies, Larenza and Paula, M. and Thormann, Wolfgang and Braun, Christina},
language = {eng},
isbn = {1467-2987},
doi = {10.1016/j.vaa.2020.04.018},
year = {2021},
date = {2021-03},
abstract = {{Objective{\textless}br{\textgreater}To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.{\textless}br{\textgreater}Study design{\textless}br{\textgreater}Prospective single-group interventional study.{\textless}br{\textgreater}Animals{\textless}br{\textgreater}A group of six healthy adult research ponies (four mares, two geldings).{\textless}br{\textgreater}Methods{\textless}br{\textgreater}Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg{\textendash}1) and butorphanol (0.01 mg kg{\textendash}1) for an unrelated study. Additional IV detomidine (0.004 mg kg{\textendash}1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg{\textendash}1) and ketamine (2.2 mg kg{\textendash}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{\textendash}1) with fenpipramide (0.0125 mg kg{\textendash}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 $\pm$ standard deviation or median and interquartile range (p {\textless} 0.05).{\textless}br{\textgreater}Results{\textless}br{\textgreater}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 $\pm$ 18.0 minutes, volume of distribution 0.43 $\pm$ 0.12 L kg{\textendash}1 and plasma clearance 7.77 $\pm$ 1.98 mL minute{\textendash}1 kg{\textendash}1. Mean arterial blood pressure increased from 85 ($\pm$16) at baseline to 100 ($\pm$26) 10 minutes after l-methadone/fenpipramide administration (p {\textequals} 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration.{\textless}br{\textgreater}Conclusions and clinical relevance{\textless}br{\textgreater}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.}},
journal = {{Veterinary Anaesthesia and Analgesia}},
volume = {48},
number = {2},
pages = {213--222},
}