Pharmacokinetics and metabolism of orally administered firocoxib, a novel second generation coxib, in horses.
The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the elimination half-life was 34 h. The area under the curve [AUC(0-tlast)] was 1.8 microg.h/mL for the oral dose and 2.3 microg.h/mL for the intravenous dose. Firocoxib was widely distributed with a volume of distribution value of 1.7 L/kg for the intravenous dose. Biotransformation of firocoxib was via dealkylation and glucuronidation to inactive metabolites, namely descyclopropylmethylfirocoxib and its glucuronide conjugate. Urinary excretion was the major route of elimination, and the clearance rate was 37 mL/h/kg.
Kvaternick
V
V
Pharmacokinetics and Drug Metabolism, Merial Limited, North Brunswick, NJ 08902, USA. valerie.kvaternick@merial.com
Pollmeier
M
M
Fischer
J
J
Hanson
P D
PD
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D052246:Cyclooxygenase 2 Inhibitors; D013450:Sulfones; D015107:4-Butyrolactone; C487384:firocoxib