Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses.
OBJECTIVE
To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally.


METHODS
6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2.


METHODS
In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed.


RESULTS
Mean +/- SD clearance and steady-state volume of distribution of firocoxib were 40.5 +/- 14.7 mL/h/kg and 2.3 +/- 0.7 L/kg, respectively. Mean half-life was 44.2 +/- 21.6 hours and 36.5 +/- 9.5 hours for IV and oral administration, respectively. The urine concentration- time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 +/- 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance.


CONCLUSIONS
The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.
Letendre
Laura T
LT
Merial Ltd, 3239 Satellite Blvd, Duluth, GA 30096, USA.
Tessman
Ronald K
RK
McClure
Scott R
SR
Kvaternick
Valerie J
VJ
Fischer
James B
JB
Hanson
Peter D
PD
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000662:veterinary
D013450:Sulfones; D015107:4-Butyrolactone; C487384:firocoxib