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

Abstract

ObjectivesTo determine the sedative effects and pharmacokinetic profile of detomidine when administered intravaginally as a gel formulation to horses. Study designRandomized, crossover, masked experimental design. AnimalsA group of six healthy adult mares (494 ± 56 kg). MethodsMares 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. ResultsSedation 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 relevanceDetomidine gel administered intravaginally resulted in clinically important sedation and is a viable method for detomidine gel delivery in mares.