Novel Analgesics and the Impact of Route of Administration in the Horse

Abstract

primary goal of this dissertation was to describe the disposition of novel analgesics and the impact of their administration on the equine patient. In order to support this aim, a novel, non-septic, transient model of peritonitis was characterized for use in evaluating drug movement in an inflamed abdomen. Using acetaminophen as a marker of oral drug absorption, the impacts of both route (nasogastric tube administration vs. syringe) and volume (1.5 L vs. 100 mL) administered on drug disposition were compared. From this, placement of a nasogastric tube and larger volumes of water used for dissolution improved absorption of acetaminophen. Firocoxib was used to evaluate formulation effect on oral absorption. From this, it was determined that both the canine chewable tablet and equine paste were found to be equally bioavailable. Zonisamide was evaluated in a simple crossover study to assess both oral and rectal administration of the anti-epileptic drug. A pharmacokinetic profile was generated for oral route; however, the active ingredient did not prove to be rectally absorbed. Finally, two cannabidiol products were profiled after both oral and transmucosal administration. Consistent with human and canine studies, it appears transmucosal administration improves absorption of the product and lends itself for further work. Overall, this dissertation demonstrates the importance of scientifically studying both route and formulation prior to administration to the equine patient rather than making assumptions of drug movement based on work performed in other species.