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  • Author or Editor: Jill K. Giri x
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Objective—To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses.

Animals—6 adult horses.

Procedures—A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined.

Results—Mild clinical effects, including tachycardia and muscle fasciculations, were observed during drug administration but stopped at the end of the infusion. Pirfenidone and 2 metabolites, hydroxypirfenidone and carboxypirfenidone, were detected by the end of the 5-minute infusion. Mean peak plasma concentration of pirfenidone was 182.5 μmol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 μmol/L, respectively, at 40 minutes after infusion. No parent drug or metabolites were detected at 24 hours. Distribution of pirfenidone best fit a 2-compartment model, and the drug had mean ± SEM elimination half-life of 86.0 ± 4.7 minutes, mean body clearance of 6.54 ± 0.45 mL/kg/min, and apparent volume of distribution at steady state of 0.791 ± 0.056 L/kg.

Conclusions and Clinical Relevance—Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.

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in American Journal of Veterinary Research