The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys (Equus africanus asinus). Academic Article uri icon

abstract

  • 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; P < 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 (P 0.038) and 3 to 15 minutes (P 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.

published proceedings

  • Can J Vet Res

author list (cited authors)

  • O, O., Simon, B. T., Ebner, L. S., Lizarraga, I., Sun, X., & Cox, S. K.

citation count

  • 1

complete list of authors

  • O, Odette||Simon, Bradley T||Ebner, Lisa S||Lizarraga, Ignacio||Sun, Xiaocun||Cox, Sherry K

publication date

  • April 2022