Abstract
Objectives
To determine the sedative effects and pharmacokinetic profile of detomidine when administered
intravaginally as a gel formulation to horses.
Study design
Randomized, crossover, masked experimental design.
Animals
A group of six healthy adult mares (494 ± 56 kg).
Methods
Mares were studied on two occasions and were administered either detomidine hydrochloride
(10 μg kg–1) intravenously (treatment IV) or detomidine gel (40 μg kg–1) intravaginally (treatment IVG), separated by 1 week. Sedation, ataxia, muzzle–floor
distance and heart rate (HR) were evaluated every 15 minutes for 240 minutes. Venous
blood samples were collected at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360
minutes postadministration and were analyzed for detomidine and metabolites using
liquid chromatography–tandem mass spectrometry. Measured variables were compared over
time and between treatments using mixed model analysis. Correlation between drug plasma
concentrations and muzzle–floor distance, and sedation and ataxia scores was determined
using the Spearman correlation coefficient. Data are presented as mean ± standard
error of the mean and p value was set at <0.05.
Results
Sedation was shorter with IV (119 ± 16 minutes) than with IVG (188 ± 22 minutes).
Ataxia scores remained greater than baseline for 90 and 135 minutes for treatments
IV and IVG, respectively. HR was lower than baseline for 45 and 30 minutes for IV
and IVG, respectively, but did not differ between treatments. The mean maximum plasma
concentration of detomidine, time to maximum concentration and bioavailability for
treatment IVG was 8.57 ng mL–1, 0.37 hour and 25%, respectively. There was a significant correlation (r = 0.68)
between plasma detomidine concentrations and sedation score.
Conclusions and clinical relevance
Detomidine gel administered intravaginally resulted in clinically important sedation
and is a viable method for detomidine gel delivery in mares.
Keywords
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Article info
Publication history
Published online: June 17, 2019
Accepted:
June 2,
2019
Received:
December 16,
2018
Identification
Copyright
Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia.
