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Pharmacokinetics of midazolam after intravenous administration to horses
Author(s) -
Hubbell J. A. E.,
Kelly E. M.,
Aarnes T. K.,
Bednarski R. M.,
Lerche P.,
Liu Z.,
Lakritz J.
Publication year - 2013
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12049
Subject(s) - midazolam , pharmacokinetics , volume of distribution , crossover study , sedation , horse , anesthesia , medicine , sedative , volunteer , respiratory system , chemistry , pharmacology , biology , paleontology , alternative medicine , pathology , agronomy , placebo
Summary Reasons for performing the study Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. Objective To determine the pharmacokinetics and sedative effects of midazolam in horses. Study design Blinded, randomised, crossover design. Methods 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. Results 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. Conclusions 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. Potential relevance Midazolam produces muscle relaxation but not sedation in adult horses.