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In vitro anti‐ LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses
Author(s) -
Bianco A. W.,
Moore G. E.,
Cooper B. R.,
Taylor S. D.
Publication year - 2018
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/jvp.12425
Subject(s) - ketorolac tromethamine , pharmacology , in vivo , medicine , eicosanoid , dose , crossover study , ibuprofen , thromboxane b2 , chemistry , analgesic , ketorolac , placebo , arachidonic acid , biology , biochemistry , platelet , alternative medicine , microbiology and biotechnology , pathology , enzyme
Flunixin meglumine ( FM ) is a commonly used Nonsteroidal anti‐inflammatory drug ( NSAID ) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine ( KT ) demonstrates superior efficacy compared to other NSAID s in humans, but its anti‐inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide ( LPS )‐induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM . Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS ‐induced Thromboxane B 2 ( TXB 2 ) and Prostaglandin E 2 ( PGE 2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS ‐induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti‐inflammatory and analgesic effects of KT is warranted.