Pharmacokinetics of orally administered pirfenidone in male and female beagles.
Pirfenidone, a promising antifibrotic agent, was administered orally to dogs at 0, 40, 140, and 400 mg/kg/day. Serum was collected for pirfenidone assay at 0, 26 and 39 weeks of treatment. From the pirfenidone concentrations, pharmacokinetic parameters were determined for each dog at each treatment interval. The only significant differences because of gender were for concentration maxima. Unsurprisingly, there were many significant differences because of dose in concentration maximum and area under curve (AUC), and significant, positive linear correlations of both parameters with dose. There were few significant differences in time of maximal concentration and no correlation with dose. The mean +/- SE clearances were 1.99 +/- 0.13, 1.64 +/- 0.13 and 1.78 +/- 0.14 L/h/kg for doses of 40, 140, and 400 mg/kg, respectively, with no significant differences attributable to dose. There was an unexplained pattern in maximal concentration and AUC with regard to duration of treatment, with the parameters being highest at week 0, lowest at week 26, and intermediate at week 39. Clearance had the reverse pattern; time of maximal concentration had no pattern.
Bruss
M L
ML
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. mlbruss@ucdavis.edu
Margolin
S B
SB
Giri
S N
SN
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004285:Dogs / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D008297:Male; D011728:Pyridones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D011728:Pyridones; D014409:Tumor Necrosis Factor-alpha; C093844:pirfenidone