title: Pharmacokinetics and clinical effects of pirfenidone administered intravenously in horses.
abstract: 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.
authors.affiliation: Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Amy E Poulin
authors.initials: AE
authors.lastname: Braim
authors.forename: Melinda H
authors.initials: MH
authors.lastname: Macdonald
authors.forename: Michael L
authors.initials: ML
authors.lastname: Bruss
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
authors.forename: Jill K
authors.initials: JK
authors.lastname: Giri
authors.forename: Shri N
authors.initials: SN
authors.lastname: Giri
mesh_terms: 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
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone