Pirfenidone, a unique experimental drug with anti-fibrotic and anti-inflammatory properties, afforded no apparent therapeutic benefit in horses with experimentally-induced endotoxemia, leaving Cal Davis researchers rather disappointed.
"Previous studies led us to believe that pirfenidone would minimize the effects of circulating lipopolysaccharide and inhibit the production of the pro-inflammatory cytokine tumor necrosis factor-alpha in endotoxic horses," explained lead researcher Melinda MacDonald, DVM, PhD, from the departments of surgery and radiology at the university's College of Veterinary Medicine.
Endotoxemia is a leading cause of morbidity and is associated with high mortality rates in horses of all ages.
"Despite decades or intensive research, there is no dependable method of prevention or reliably effective treatment for affected horses," said MacDonald.
MacDonald and colleagues administered pirfenidone intravenously to adult horses after administering a low dose of endotoxin. The drug failed to moderate the development of clinical signs of endotoxemia, or to suppress tumor necrosis factor alpha concentrations in the horses, forcing the researchers to report the apparent failure of the drug in this model of endotoxemia.
They had expected a more profound effect based on the studies performed in other species with endotoxemia.
To add insult to injury, the dose of pirfenidone used in these horses had excitatory effects that, according to the report, occurred too frequently and dramatically to consider use of the same dose in clinical cases.
"There is a strong incentive to identify effective treatment protocols and increase survival rates," added MacDonald. "Further studies using related or more potent drugs and to examine the effect of oral or topical formulations of pirfenidone for the management of other conditions may be warranted."
The study, "Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia," was published in the August 2009 edition of the American Journal of Veterinary Research. The abstract is available on PubMed.
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