Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies.
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.
['Gittel|Claudia|C|', 'Schulz-Kornas|Ellen|E|', 'Sandbaumhüter|Friederike A|FA|', 'Theurillat|Regula|R|', 'Vervuert|Ingrid|I|', 'Larenza Menzies|M Paula|MP|', 'Thormann|Wolfgang|W|', 'Braun|Christina|C|']
D000818:Animals D005260:Female D006339:Heart Rate D006736:Horses D007530:Isoflurane D007649:Ketamine D008297:Male D008691:Methadone D011446:Prospective Studies D012121:Respiration, Artificial
isoflurane anaesthesia fasciculation horse balanced anaesthesia opioids