Pharmacokinetics of Detomidine and Vatinoxan in Horses

The pharmacokinetics of detomidine, vatinoxan, and their combination have not been previously characterized in detail in horses. Detomidine (20 μg/kg), vatinoxan (200 μg/kg), or their combination was administered intravenously to six horses according to a Latin square design. Blood was sampled at various times up to 480 min following administration. Plasma concentrations of detomidine, OH-detomidine, COOH-detomidine, and vatinoxan were measured using liquid chromatography/tandem mass spectrometry. Compartmental models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A 5-compartment model provided the best fit for detomidine and its metabolites, whereas the disposition of vatinoxan was best described by a 3-compartment model. The volume of distribution at steady state was 762 mL/kg for detomidine and 1422 mL/kg for vatinoxan. Total metabolic clearance was 21.6 mL/min/kg for detomidine and 7.1 mL/min/kg for vatinoxan. Clearance of detomidine into OH-detomidine and of OH-detomidine into COOH-detomidine was predicted to be 40 and 7% of their respective clearance. Covariates accounting for the effect of vatinoxan on several parameters improved the model, suggesting that administration of vatinoxan affects the disposition of detomidine. Similarly, covariates suggested that administration of detomidine affects the disposition of vatinoxan.