Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary investigation.

This study looks into the use of Ussing chambers, typically utilised in human and rat drug testing, as a method to examine the permeability of mucosal surfaces in horses. Through this tool, the research team analysed the effectiveness of the four distinct drugs, with varying qualities and bioavailability, to determine the potential of using this technique in drug screening processes in horse with poor oral drug bioavailability.

Ussing Chambers and In Vitro/In Vivo Correlations

• The Ussing chamber has been extensively used in previous drug research relating to humans, rats and other species. It is essentially a device for measuring the transport of chemical substances through living tissue.
• In Vitro/In Vivo Correlations (IVIVC) is a predictive mathematical model that describes the relationship between in vitro data (laboratory data obtained outside the living organisms) and in vivo data (Factual data from living organisms).
• The Biopharmaceutics Classification System (BCS) is a crucial tool in the design of drug delivery systems. It classifies the drugs into four categories based on their solubility and permeability.

Drug Selection and Findings

• The study selected four distinct drugs, Cephalexin (CPX), Marbofloxacin (MAR), Metronidazole (MTZ) and Fluconazole (FCZ), to represent a broad spectrum of physicochemical properties and bioavailability in horses.
• The permeability of these drugs in horse tissue was ranked from highest to lowest as follows: MTZ > FCZ > MAR > CPX. Metronidazole was discovered to potentially cause tissue toxicity due to its decrease in tissue transepithelial resistance, which could have led to an artificial boost in its permeability.
• The least permeable drug, Cephalexin, signals a possible deficiency in active transporters that could otherwise facilitate transportation across the tissues in other species.

Correlations, Implications and Conclusion

• The permeability ratings of the four drugs showed a significant correlation with their bioavailability, the Log P (the logarithm of the partition coefficient between n-octanol and water: a measure of a molecule’s lipophilicity) and the molecular weight of the drugs.
• These correlating factors provide detailed insights into which physicochemical properties might affect drug permeability in equine tissue and the bioavailability of the drug.
• Overall, the study suggests that the Ussing chambers might have potential as a method for determining mucosal permeability in equine drug analysis, contributing to the possibility of more effective drug screening and development in horses with poor oral bioavailability.