Pharmacokinetics of midazolam after intravenous administration to horses

Reasons for performing the studyMidazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. ObjectiveTo determine the pharmacokinetics and sedative effects of midazolam in horses. Study designBlinded, randomised, crossover design. MethodsMidazolam was administered i.v. at either 0.05 or 0.1mg/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 24h 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. ResultsPharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6ml/min/kg (range 6.1-15.2ml/min/kg) and 10.4ml/min/kg (range 8.4-17.6ml/min/kg), and median volume of distribution at steady state was 2094ml/kg (range 2076-2413ml/kg) and 2822ml/kg (range 2270-7064ml/kg) after the 0.05mg/kg and 0.1mg/kg bwt doses, respectively. Median distribution half-life was 24min (range 6-42min) and 39min (range 33.6-72min) and median terminal half-life was 216min (range 120-248min) and 408min (range 192-924min) after the 0.05mg/kg and 0.1mg/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 0.1mg/kg bwt dose. ConclusionsMidazolam 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 relevanceMidazolam produces muscle relaxation but not sedation in adult horses.