Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses.
Authors: Thomasy S M, Mama K R, Whitley K, Steffey E P, Stanley S D
Journal: Equine veterinary journal
Summary
# Editorial Summary: Fentanyl Pharmacokinetics During Equine Anaesthesia Fentanyl's potential as an adjunct to inhalant anaesthesia in horses depends on understanding how the drug behaves in the equine body, particularly under general anaesthesia—yet this information was largely absent from the literature. Thomasy and colleagues administered a single 4 µg/kg intravenous dose of fentanyl to four horses in both awake and isoflurane-anaesthetised states using a crossover design, measuring plasma concentrations of fentanyl and its primary metabolite (PMA) via liquid chromatography-mass spectrometry. Isoflurane anaesthesia significantly reduced fentanyl clearance and volume of distribution, extending the drug's effects; the half-life remained approximately 1 hour in both states, but the metabolite (PMA) clearance and distribution were also substantially reduced under anaesthesia, with half-lives of 2 hours awake versus 1.5 hours anaesthetised. These findings are crucial for practitioners using fentanyl infusions during equine surgery, as standard loading and maintenance doses developed in awake horses may result in excessive accumulation and prolonged recovery times when administered during isoflurane anaesthesia—necessitating dose adjustments based on the anaesthetic state to maintain consistent therapeutic effects whilst minimising overdosage.
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Practical Takeaways
- •Fentanyl dosing and infusion rates need adjustment when horses are under isoflurane anaesthesia due to reduced drug clearance; standard awake dosing may result in excessive accumulation
- •The shorter PMA elimination half-life under anaesthesia suggests metabolite accumulation may be less problematic than expected during extended procedures
- •These pharmacokinetic data should inform loading doses and infusion protocols when using fentanyl as an adjunct to isoflurane anaesthesia in equine practice
Key Findings
- •Isoflurane anaesthesia significantly decreased fentanyl clearance compared to awake horses (P < 0.05)
- •Fentanyl elimination half-life was 1 hour in both awake and anaesthetised horses, but volume of distribution decreased from 0.37 to 0.26 l/kg with anaesthesia
- •PMA (fentanyl metabolite) elimination half-life decreased from 2 hours in awake horses to 1.5 hours in anaesthetised horses
- •Isoflurane significantly decreased both PMA apparent clearance and volume of distribution