Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia.
OBJECTIVE
To characterize effects of IV administration of pirfenidone on clinical, biochemical, and hematologic variables and circulating tumor necrosis factor (TNF)-alpha concentrations in horses after infusion of a low dose of endotoxin.


METHODS
18 healthy adult horses.


METHODS
Horses were randomly assigned to 3 groups (n = 6 horses/group) and administered an IV infusion of 30 ng of endotoxin/kg or saline (0.9% NaCl) solution during a 30-minute period. Lipopolysaccharide-pirfenidone horses received endotoxin followed by pirfenidone (loading dose of 11.6 mg/kg and then constant rate infusion [CRI] at 9.9 mg/kg/h for 3 hours). Lipopolysaccharide-saline horses received endotoxin followed by infusion (loading dose and CRI for 3 hours) of saline solution. Saline-pirfenidone horses received saline solution followed by pirfenidone (loading dose and then CRI for 3 hours). Physical examination variables were recorded and blood samples collected at predetermined intervals throughout the 24-hour study period. Blood samples were used for CBCs, biochemical analyses, and determinations of TNF-alpha concentrations.


RESULTS
IV infusion of pirfenidone after administration of a low dose of endotoxin failed to attenuate the clinical, clinicopathologic, or cytokine alterations that developed secondary to endotoxin exposure. Intravenous infusion of pirfenidone after administration of saline solution induced mild transient clinical signs, but associated clinicopathologic changes were not detected.


CONCLUSIONS
IV administration of pirfenidone was tolerated with only mild transient clinical adverse effects during infusion. However, administration of pirfenidone did not protect horses from the systemic effects of experimentally induced endotoxemia. Further studies of related, but more potent, drugs may be warranted.
Poulin Braim
Amy E
AE
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
MacDonald
Melinda H
MH
Bruss
Michael L
ML
Grattendick
Ken J
KJ
Giri
Shri N
SN
Margolin
Solomon B
SB
D000704:Analysis of Variance; D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy / Q000662:veterinary*; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007275:Injections, Intravenous / Q000662:veterinary; D008070:Lipopolysaccharides; D008297:Male; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D008070:Lipopolysaccharides; D011728:Pyridones; D014409:Tumor Necrosis Factor-alpha; C093844:pirfenidone