Pharmacokinetics of midazolam after intravenous administration to horses.
Authors: Hubbell J A E, Kelly E M, Aarnes T K, Bednarski R M, Lerche P, Liu Z, Lakritz J
Journal: Equine veterinary journal
Summary
# Pharmacokinetics of Midazolam in Horses: Understanding Drug Behaviour and Clinical Effects Midazolam's use in equine practice for seizure control and muscle relaxation has lacked pharmacokinetic characterisation, prompting Hubbell and colleagues to investigate how horses metabolise and respond to the drug. Using a crossover design, six horses received intravenous midazolam at either 0.05 or 0.1 mg/kg on separate occasions, with serum drug concentrations tracked over 24 hours and behavioural observations recorded throughout. The higher dose produced notably prolonged elimination (terminal half-life of 408 minutes versus 216 minutes at the lower dose), alongside greater individual variability in clearance and distribution, whilst importantly, neither dose induced sedation—instead manifesting as dose-dependent ataxia, postural sway, weakness and recumbency in one horse at 0.1 mg/kg. These findings clarify that midazolam operates as a muscle relaxant rather than a sedative in adult horses, with drug redistribution—not hepatic metabolism alone—terminating its clinical effects, which has direct implications for dosing protocols and the realistic expectations when using this agent perioperatively or in seizure management. Practitioners should anticipate brief incoordination rather than sedation and exercise caution with higher doses given the risk of profound ataxia and recumbency, particularly when combined with other agents or in compromised patients where clearance might be further impaired.
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Practical Takeaways
- •Midazolam causes muscle relaxation and ataxia in horses but does not produce sedation, making it unsuitable as a standalone sedative agent
- •The 0.1 mg/kg dose carries risk of recumbency and severe ataxia; careful dose selection and monitoring are essential if used clinically
- •Prolonged terminal half-life (3-7 hours) means effects persist longer than initial clinical signs suggest; allow adequate recovery time post-administration
Key Findings
- •Midazolam total clearance was 10.6 ml/min/kg at 0.05 mg/kg dose and 10.4 ml/min/kg at 0.1 mg/kg dose, with minimal dose-dependent variation
- •Terminal half-life was 216 min (0.05 mg/kg) and 408 min (0.1 mg/kg), indicating dose-dependent pharmacokinetics with longer elimination at higher doses
- •Midazolam produced ataxia, postural sway, and weakness but no sedation; one horse became recumbent at 0.1 mg/kg dose
- •Drug redistribution is the primary mechanism for effect termination rather than metabolism