In vitro anti-LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses.

This study is about assessing the dosage and safety of Ketorolac tromethamine (KT), a type of Nonsteroidal anti-inflammatory drug (NSAID), on horses in vitro (in a lab environment), comparing its effects to another NSAID, Flunixin Meglumine (FM), and evaluating the safety of its repeated dosage.

Objectives of the Research

• The main purpose of the study was to conduct a dosage determination study. The aim was to confirm if a previously used dosage of KT could effectively suppress Lipopolysaccharide (LPS)-induced eicosanoid production in horses in the lab. Eicosanoids are signaling molecules produced by oxidation of fatty acids, involved in inflammation. Lipopolysaccharides (LPS) act as endotoxins and trigger immune responses.
• The suppression effects of KT on eicosanoids were compared to the effects of FM.
• The second part of the study revolved around administering and testing the two drugs, KT and FM in nine healthy horses to evaluate their plasma concentrations.
• The third objective was to assess the safety of repeated dosages of KT. This was important as there was no existing data on the safety of repeated KT doses in horses.

Research Design and Methodology

• The researchers set up a randomized crossover study involving nine healthy horses. Randomization and crossover design help to eliminate inherent differences (physical, genetic etc.) among horses that could potentially interfere with the results.
• Dosages of 0.5 mg/kg of KT and 1.1 mg/kg of FM were used for this experiment.
• The researchers were keen to observe any negative health effects of the drugs, which would indicate their respective safety profiles when administered repeatedly over a period.

Key Findings

• Both KT and FM were found to suppress LPS-induced Thromboxane B (TXB) and Prostaglandin E (PGE) production for up to twelve hours. TXB and PGE are types of inflammatory eicosanoids.
• IV administration resulted in plasma concentrations of KT and FM similar to previous studies, affirming the consistency of their absorption rates in the body.
• Importantly, there were no observable adverse effects in the horses, leading to the conclusion that repeated dosing of KT up to 3 days appears safe for healthy horses.

Implications

• The in vitro results have contributed to the dosage determination of KT for horses, providing reassurance on its ability to inhibit LPS-induced eicosanoids.
• No adverse effects were noticed during the study which suggests the safety of repeated dosing of KT on horses. This is very important information for veterinarians and equine managers.
• This research paves the way for further investigations on the anti-inflammatory and analgesic effects of KT in animals, specifically in horses. If proven safe and effective, KT could be a viable substitute for or addition to other NSAIDs like FM in equine medication.