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Mucosal permeability of water‐soluble drugs in the equine jejunum: a preliminary investigation
Author(s) -
DAVIS J. L.,
LITTLE D.,
BLIKSLAGER A. T.,
PAPICH M. G.
Publication year - 2006
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2006.00757.x
Subject(s) - bioavailability , biopharmaceutics classification system , pharmacology , intestinal permeability , ussing chamber , in vivo , pharmacokinetics , chemistry , horse , metronidazole , ketoprofen , in vitro , medicine , biology , antibiotics , biochemistry , microbiology and biotechnology , paleontology
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 before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioavailability in the horse. Permeability was ranked as follows: MTZ > FCZ > MAR > CPX. This correlated with the bioavailability ( R 2 = 0.633447), the Log P ( R 2 = 0.648517), as well as the molecular weight ( R 2 = 0.851208) of the drugs. Metronidazole induced a decrease in the tissue transepithelial resistance, suggestive of the possibility of tissue toxicity, which may have falsely increased its permeability. 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 promising method for determining mucosal permeability in the horse.