Presenter: Jennifer L. Davis
Advisor(s): Mark G. Papich
Author(s): Jennifer L. Davis, Anthony T. Blikslager, Dianne Little and Mark G. Papich
Graduate Program: Comparative Biomedical Sciences

Title: Mucosal Permeability of Water-Soluble Drugs in the Equine Jejunum: A Preliminary Investigation

Abstract: Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to develop in vitro/in vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs prior to development to determine if they warrant further study. The purpose of this study was to examine the feasability of using the Ussing chamber to study the mucosal permeability of commonly used antimicrobial drugs in the equine jejunum. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen based on the wide range of physicochemical properties and oral bioavailability in the horse. Permeability was ranked as follows: MTZ>FCZ>MAR>CPX. This correlated with the bioavailability (R2 = 0.633447), the LogP (R2 = 0.648517), as well as the molecular weight (R2 = 0.851208) of the drugs. Metronidazole induced a decrease in the transepithelial resistance across the tissue, possibly by causing a direct cytotoxic effect, which may have falsely increased its permeability. Due to its low molecular weight, permeability of metronidazole may also have been increased due to paracellular transport of the drug. The low permeability of cephalexin across the tissue may indicate a lack of active transporters that are found in other species. From this study, we can conclude that the Ussing chamber is a viable method for determining mucosal permeability in the horse.