In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses |
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| Authors: | A W Bianco G E Moore B R Cooper S D Taylor |
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| Affiliation: | 1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA;2. Department of Veterinary Administration, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA;3. Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA |
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| Abstract: | 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 NSAIDs 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 B2 (TXB2) and Prostaglandin E2 (PGE2) 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. |
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| Keywords: | horse ketorolac prostaglandin safety thromboxane |
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