title: In vitro and ex vivo pharmacodynamics of selected non-steroidal anti-inflammatory drugs in equine whole blood.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenases (COX), and the inhibition of COX-2 rather than COX-1 can limit the onset of NSAID-related adverse effects. The pharmacodynamic properties of eltenac, naproxen, tepoxalin, SC-560 and NS 398 in healthy horses were investigated using an in vitro whole blood assay. To predict COX selectivity in clinical use, eltenac and naproxen were also studied ex vivo after intravenous administration. SC-560 acted as a selective COX-1 inhibitor, tepoxalin as a dual inhibitor with potent activity against COX-1, and NS 398 as a preferential COX-2 inhibitor. Eltenac was a preferential COX-2 inhibitor in vitro but un-selective in the ex vivo study. Naproxen maintained its non-selectivity both in vitro and ex vivo. These findings have demonstrated that in vitro studies may not accurately predict in vivo NSAID selectivity for COX and should be confirmed using an ex vivo whole blood assay.
authors.affiliation: Pharmacology and Toxicology Division, Department of Animal Pathology, Faculty of Veterinary Medicine, University of Turin, Italy. barbara.cuniberti@unito.it
authors.forename: B
authors.initials: B
authors.lastname: Cuniberti
authors.forename: R
authors.initials: R
authors.lastname: Odore
authors.forename: R
authors.initials: R
authors.lastname: Barbero
authors.forename: P
authors.initials: P
authors.lastname: Cagnardi
authors.forename: P
authors.initials: P
authors.lastname: Badino
authors.forename: C
authors.initials: C
authors.lastname: Girardi
authors.forename: G
authors.initials: G
authors.lastname: Re
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000493:pharmacokinetics*; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D005260:Female; D006736:Horses / Q000097:blood*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases