Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies.
Abstract: To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies. Methods: Prospective single-group interventional study. Methods: A group of six healthy adult research ponies (four mares, two geldings). Methods: Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg) and butorphanol (0.01 mg kg) for an unrelated study. Additional IV detomidine (0.004 mg kg) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg) and ketamine (2.2 mg kg). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg) with fenpipramide (0.0125 mg kg) 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 and plasma clearance 7.77 ± 1.98 mL minute kg. 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: 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.
Publication Date: 2020-12-09 PubMed ID: 33423953DOI: 10.1016/j.vaa.2020.04.018Google Scholar: Lookup
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Summary
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The study aims to examine the behavior and selected effects of a commercial l-methadone/fenpipramide drug combination on anaesthetized ponies. The research reveals that administrating this combo to anaesthetized ponies caused a temporary increase in blood pressure, but it didn’t affect the heart rate and showed similar pharmacokinetic behavior to conscious horses given racemic methadone.
Objective and Methodology
- The objective of this experiment was to study the pharmacokinetics (how the body absorbs, distributes, metabolizes, and excretes a drug) and some pharmacodynamic effects (the biochemical and physiological effects of a drug) of a commercially available l-methadone/fenpipramide combination on ponies anaesthetized with isoflurane (an inhalation anesthetic).
- The method employed here was an interventional study involving six healthy adult research ponies. The ponies were sedated and subsequently anaesthetized for a separate, unrelated study which provided the opportunity for the l-methadone/fenpipramide analysis.
- Once the ponies were under stable isoflurane anaesthesia, they received an intravenous (IV) administration of l-methadone (a potent opioid) and fenpipramide (a drug used to treat irregular heartbeat). Various cardiorespiratory variables were recorded every 10 minutes and compared with the baseline readings taken before the drug administration.
- Besides, arterial plasma samples were collected at specific time intervals to analyze the plasma concentrations, and thus the pharmacokinetics, of l-methadone.
Results and Findings
- From the collected data, it was observed that the plasma concentration of l-methadone followed a two-phase distribution. There was a rapid initial distribution phase followed by a slower elimination phase. These patterns of distribution and elimination have been described using a two-compartment model.
- The terminal half-life of l-methadone, which is the time taken for the drug’s concentration to fall to half in the blood plasma, was about 44.3 minutes, volume of distribution was 0.43 L/kg, and plasma clearance was 7.77 mL/minute/kg.
- After the administration of l-methadone/fenpipramide, a notable increase was tracked in the mean arterial blood pressure, but the heart rate remained stable. However, muscle fasciculations (brief, spontaneous contractions affecting a small number of muscle fibers) were observed in two ponies at different times following the l-methadone administration.
Conclusions
- In conclusion, the study determines that giving a l-methadone/fenpipramide combination to isoflurane-anaesthetized ponies resulted in a short-term increase in blood pressure with no concurrent rise in heart rate.
- The pharmacokinetics of l-methadone in this scenario matched those reported for conscious horses given a racemic (equal proportion mixture) of methadone. This congruence suggests that whether the horse is conscious or anaesthetized doesn’t significantly affect the manner in which l-methadone is metabolized and eliminated from the body.
Cite This Article
APA
Gittel C, Schulz-Kornas E, Sandbaumhüter FA, Theurillat R, Vervuert I, Larenza Menzies MP, Thormann W, Braun C.
(2020).
Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies.
Vet Anaesth Analg, 48(2), 213-222.
https://doi.org/10.1016/j.vaa.2020.04.018 Publication
Researcher Affiliations
- Department for Horses, University of Leipzig, Leipzig, Germany; Queen's Veterinary School Hospital, University of Cambridge, Cambridge, UK. Electronic address: csg39@cam.ac.uk.
- Max Planck Weizmann Center for Integrative Archaeology and Anthropology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
- Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
- Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
- Institute of Animal Nutrition, Nutrition Diseases and Dietetics, University of Leipzig, Leipzig, Germany.
- Clinical Unit of Anaesthesiology and Perioperative Intensive-Care Medicine, Vetmeduni Vienna, Vienna, Austria.
- Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
- Clinical Unit of Anaesthesiology and Perioperative Intensive-Care Medicine, Vetmeduni Vienna, Vienna, Austria.
MeSH Terms
- Animals
- Female
- Heart Rate
- Horses
- Isoflurane
- Ketamine
- Male
- Methadone / pharmacology
- Prospective Studies
- Respiration, Artificial / veterinary
Citations
This article has been cited 1 times.- Sandbaumhüter FA, Gittel C, Larenza-Menzies MP, Theurillat R, Thormann W, Braun C. Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis.. Electrophoresis 2021 Sep;42(17-18):1826-1831.
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