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In addition to its antimicrobial properties, tulathromycin demonstrates immune-modulating and anti-inflammatory actions in experimental studies. In bovine polymorphonuclear cells (PMNs; neutrophils), tulathromycin promotes apoptosis (programmed cell death) and the clearance of apoptotic cells by macrophages. It lowers the production of the pro-inflammatory mediators leukotriene B4 and CXCL-8 and induces the production of anti-inflammatory and pro-resolving lipid lipoxin A4.
Ketoprofen is a substance belonging to the group non-steroidal anti-inflammatory drugs (NSAIDs). Ketoprofen has anti-inflammatory, analgesic and antipyretic properties. Not all aspects of its mechanism of action are known. Effects are obtained partially by the inhibition of prostaglandin and leukotriene synthesis by ketoprofen, acting on cyclooxygenase and lipoxygenase respectively. The formation of bradykinin is also inhibited. Ketoprofen inhibits thrombocyte aggregation.
When subcutaneously co-administered in the combination formulation, at 2.5 mg tulathromycin/kg bodyweight, the maximum concentration (Cmax) in plasma was approximately 0.4 μg/ml, this was achieved approximately 3 hours post-dosing (Tmax). Peak concentrations were followed by a slow decline in systemic exposure with an apparent elimination half-life (t1/2) of 85 hours in plasma.
Furthermore, after subcutaneous injection of the tulathromycin-ketoprofen combination, the AUC0-t of tulathromycin has been shown to be bioequivalent to the AUC0-t after subcutaneous injection of tulathromycin 100 mg/ml for cattle. The combination had a slightly lower tulathromycin Cmax and the rate of absorption was decreased in comparison with the administration of the compounds separately.
Regarding ketoprofen, following administration of the combination product, at 3 mg ketoprofen/kg bodyweight, the pharmacokinetics of ketoprofen are driven by flip-flop kinetics. The mean Cmax in plasma was 2 μg/ml, which was achieved at 4 hours on average. The terminal half-life of ketoprofen is dominated by the slow absorption and was estimated at 6.8 hours.
Furthermore, after subcutaneous injection of the tulathromycin-ketoprofen combination, there was a delay in the absorption, with a lower ketoprofen peak concentration, and a longer elimination half-live, as compared with the compound alone.