EXPERIMENTAL AND BASIC RESEARCH STUDIES
Pharmacokinetics of midazolam after intravenous administration to horses
Article first published online: 12 MAR 2013
© 2013 EVJ Ltd
Equine Veterinary Journal
Volume 45, Issue 6, pages 721–725, November 2013
How to Cite
Hubbell, J. A. E., Kelly, E. M., Aarnes, T. K., Bednarski, R. M., Lerche, P., Liu, Z. and Lakritz, J. (2013), Pharmacokinetics of midazolam after intravenous administration to horses. Equine Veterinary Journal, 45: 721–725. doi: 10.1111/evj.12049
- Issue published online: 14 OCT 2013
- Article first published online: 12 MAR 2013
- Accepted manuscript online: 14 JAN 2013 09:11AM EST
- Manuscript Accepted: 4 JAN 2013
- Manuscript Received: 2 JUL 2012
- College of Veterinary Medicine
Reasons for performing the study
Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown.
To determine the pharmacokinetics and sedative effects of midazolam in horses.
Blinded, randomised, crossover design.
Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectrometry method. Heart and respiratory rates and indices of sedation, ataxia, and sensitivity to stimuli were recorded before and at predetermined times after midazolam administration.
Pharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6 ml/min/kg (range 6.1–15.2 ml/min/kg) and 10.4 ml/min/kg (range 8.4–17.6 ml/min/kg), and median volume of distribution at steady state was 2094 ml/kg (range 2076–2413 ml/kg) and 2822 ml/kg (range 2270–7064 ml/kg) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Median distribution half-life was 24 min (range 6–42 min) and 39 min (range 33.6–72 min) and median terminal half-life was 216 min (range 120–248 min) and 408 min (range 192–924 min) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Cardiorespiratory parameters and sedation scores did not change. Midazolam caused agitation, postural sway, weakness, and one horse became recumbent after the 0.1 mg/kg bwt dose.
Midazolam produces ataxia and postural sway of short duration after i.v. administration to horses. Sedation was not evident after midazolam administration. Drug redistribution is likely the primary mechanism for the termination of effect.
Midazolam produces muscle relaxation but not sedation in adult horses.