Jula, Catherine Antonia2024-08-282024-08-282024-08-27vt_gsexam:41334https://hdl.handle.net/10919/121026Few drugs are available to treat congestive heart failure and other cardiac diseases in horses. Pimobendan is an inodilator drug approved as Vetmedin® for treatment of canine cardiac disease. Previous research shows that pimobendan increases heart rate and contractility following intravenous administration in horses. The pharmacokinetics of oral pimobendan have not been investigated in horses. The hypothesis of this study was that pimobendan would be absorbed following oral administration to healthy adult horses and reach concentrations known to be therapeutic in other species. Additional objectives were to compare the absorption of compounded pimobendan capsules (C) and suspension (S) to Vetmedin® (V) and determine the effects of sample site on plasma drug concentrations in a pilot study using two horses. These two horses received C, S, or V (0.5 mg/kg via oral syringe, once) following a minimum 10 hour fast, using a crossover design with a minimum 1-week washout period. Samples were collected simultaneously from lateral thoracic and jugular catheters before and after drug administration at predetermined time points. Differences between formulation and sample site were analyzed by one-way ANOVA. After evaluation of the data from the initial 2 horses, an additional 4 horses received pimobendan, in the form of Vetmedin tablets® (V), in a similar manner. Only jugular samples were collected at the same predetermined time points. Plasma concentrations were determined by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and pharmacokinetic parameters determined by noncompartmental analysis. No significant differences were noted between formulations or sample site (P < 0.05). Concentrations in compounded formulations were 88%(S) and 90%(C) of label. For V, mean (±SD) maximum plasma concentration (Cmax) was 4.96 ± 2.13 ng/mL at 2.17 ± 0.98 hours, and area under the curve (AUC0-∞) was 22.1 ± 8.8*ng/mL. Concentration of the active metabolite of pimobendan, o-desmethyl-pimobendan, was below the limit of detection (0.07ng/mL) for all samples. At 0.5mg/kg orally, pimobendan plasma concentrations were considerably lower than reported in dogs and other species. There was no evidence of oral transmucosal absorption. Pimobendan was poorly absorbed in horses, regardless of formulation, and appears unlikely to have clinical effects.ETDenIn Copyrightequinecongestive heart failureinotropeinodilatorThesis