Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses

Reza Seddighi, Heather K Knych, Sherry K. Cox, Xiaocun Sun, Kaitlin A. Moorhead, Thomas J. Doherty

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalVeterinary Anaesthesia and Analgesia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

detomidine
sedatives
Hypnotics and Sedatives
pharmacokinetics
Horses
Pharmacokinetics
Gels
gels
sedation
horses
Ataxia
mares
heart rate
Therapeutics
Heart Rate
experimental design
Cross-Over Studies
Biological Availability
bioavailability
Mass Spectrometry

Keywords

  • detomidine
  • gel
  • intravaginal
  • mares
  • pharmacokinetics
  • sedation

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses. / Seddighi, Reza; Knych, Heather K; Cox, Sherry K.; Sun, Xiaocun; Moorhead, Kaitlin A.; Doherty, Thomas J.

In: Veterinary Anaesthesia and Analgesia, 01.01.2019.

Research output: Contribution to journalArticle

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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.",
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AU - Moorhead, Kaitlin A.

AU - Doherty, Thomas J.

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