The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys .

Can J Vet Res

Department of Clinical Sciences (O) and Department of Biomedical Sciences (Lizarraga), Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis; Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77845, USA (Simon); College of Veterinary Medicine, Lincoln Memorial University, Harrogate, Tennessee 37752, USA (Ebner); Office of Information and Technology, University of Tennessee, Knoxville, Tennessee, USA (Sun); Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA (Cox).

Published: April 2022

The pharmacokinetics and pharmacodynamics of midazolam were studied in eight 1-to-3-year-old healthy gelded donkeys. Blood samples were obtained. Heart rate, respiratory rate, rectal temperature, sedation/excitement, ataxia, and response to tactile and auditory stimuli were recorded at baseline until 48 hours after intravenous (IV) midazolam (0.1 mg/kg) administration. Plasma midazolam and 1-hydroxymidazolam were measured using reversed-phase high-performance liquid chromatography. Pharmacokinetic variables were calculated using non-compartmental analysis. Physiologic data were analyzed using a mixed-effects model followed by Dunnett's test and behavioral data were analyzed using a Friedman test then a Dunn's test; < 0.05 was considered significant. Midazolam was detectable for up to 60 minutes post-treatment in 7 donkeys. The median total body clearance, volume of distribution at steady state, elimination half-life, and area under concentration-time profile were 1210 mL/kg/h, 359 mL/kg, 0.27 hours, and 82.7 h × ng/mL, respectively. 1-hydroxymidazolam was detected (29 to 105 ng/mL) between 5 to 15 minutes post-treatment in 4 donkeys. Compared to baseline, rectal temperature and ataxia increased from 90 to 720 minutes ( ≤ 0.038) and 3 to 15 minutes ( ≤ 0.024) post-treatment, respectively. No other parameters showed statistically significant differences. Healthy donkeys cleared midazolam rapidly from plasma after IV administration. Transient ataxia and recumbency without sedation were observed.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978292PMC

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