Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses.
OBJECTIVE
To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses.


METHODS
6 adult horses.


METHODS
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 micromol/L, detected at the end of the infusion. Mean peak plasma concentrations of hydroxypirfenidone and carboxypirfenidone were 1.07 and 3.4 micromol/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
Intravenous administration of pirfenidone was tolerated with transient adverse affects during infusion, and drug clearance was rapid.
Braim
Amy E Poulin
AE
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Macdonald
Melinda H
MH
Bruss
Michael L
ML
Stanley
Scott D
SD
Giri
Jill K
JK
Giri
Shri N
SN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006736:Horses / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous / Q000662:veterinary; D008297:Male; D010865:Pilot Projects; D011728:Pyridones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012119:Respiration / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone