Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses.
Abstract: To determine the sedative effects and pharmacokinetic profile of detomidine when administered intravaginally as a gel formulation to horses. Methods: Randomized, crossover, masked experimental design. Methods: 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) intravenously (treatment IV) or detomidine gel (40 μg kg) 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, 0.37 hour and 25%, respectively. There was a significant correlation (r = 0.68) between plasma detomidine concentrations and sedation score. Conclusions: Detomidine gel administered intravaginally resulted in clinically important sedation and is a viable method for detomidine gel delivery in mares.
Published by Elsevier Ltd.
Publication Date: 2019-06-17 PubMed ID: 31474339DOI: 10.1016/j.vaa.2019.06.002Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
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The research studied the effects and pharmacokinetics of a sedative gel, detomidine, when applied intravaginally to horses. The findings suggest detomidine gel, when administered in this way, provides clinically significant sedation and can be used effectively in mares.
Research Methodology
Exploring the effects and behavior of detomidine gel when administered intravaginally to horses, the experiment utilised a group of six healthy adult mares, weighing approximately 494 ± 56 kgs.
- The experimental design was randomized, masked, and crossed-over, reported in two parts. The mares were either given detomidine hydrochloride (10 μg kg) intravenously (treatment IV) or detomidine gel (40 μg kg) intravaginally (treatment IVG), with a week’s gap between the two treatments.
- Behavioral changes like sedation, ataxia, muzzle-floor distance and heart rate (HR) were evaluated at 15-minute intervals for 240 minutes.
- Venous blood samples were collected at several time intervals post administration and were analyzed for detomidine and its metabolites using sophisticated techniques, such as liquid chromatography-tandem mass spectrometry.
Results and Analysis
The data was thoroughly analyzed over time and between treatments using mixed model analysis. Importantly, the detomidine concentrations highly corresponded with the sedation score.
- Sedation timeframes were shorter with intravenous detomidine (119 ± 16 minutes) than with intravaginal administration (188 ± 22 minutes).
- Ataxia scores, indicative of uncoordination and imbalance, remained high for a longer duration in the mares with intravaginal gel application, indicating a longer-lasting sedative effect.
- Heart rates for both treatments were lower than normal for a duration, but there was no significant difference between the two treatments.
- The mean maximum plasma concentrations, time to maximum concentration and bioavailability for detomidine gel administered intravaginally was 8.57 ng mL, 0.37 hour and 25%, respectively.
Conclusions
Conclusively, the intravaginally administered detomidine gel yielded clinically important sedation in mares. Therefore, the method was identified as a viable way of detomidine gel delivery in mares, with further implications for its practical use in a veterinary setting.
Cite This Article
APA
Seddighi R, Knych HK, Cox SK, Sun X, Moorhead KA, Doherty TJ.
(2019).
Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses.
Vet Anaesth Analg, 46(6), 772-779.
https://doi.org/10.1016/j.vaa.2019.06.002 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA. Electronic address: mrsed@utk.edu.
- K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
- Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
- Office of Information Technology, University of Tennessee, Knoxville, TN, USA.
- College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
MeSH Terms
- Administration, Intravaginal
- Animals
- Area Under Curve
- Cross-Over Studies
- Female
- Gels
- Half-Life
- Horses
- Hypnotics and Sedatives / administration & dosage
- Hypnotics and Sedatives / pharmacokinetics
- Hypnotics and Sedatives / pharmacology
- Imidazoles / administration & dosage
- Imidazoles / pharmacokinetics
- Imidazoles / pharmacology
- Injections, Intravenous
Citations
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