Disposition of firocoxib in equine plasma after an oral loading dose and a multiple dose regimen.
The objective of this study was to determine if a single loading dose (LD), 3× the label dose of firocoxib oral paste, followed by nine maintenance doses at the current label dose achieves and maintains near steady state concentrations. Six healthy, adult mares were administered 0.3mg/kg of firocoxib on Day 0, and 0.1 mg/kg 24 h later on Day 1, and at 24 h intervals from Day 2 to Day 9, for a total of 10 doses. Blood samples were collected throughout the study. The mean firocoxib maximum plasma concentration and standard deviation was 199±97 ng/mL, 175±44 ng/mL and 183±50 ng/mL after the LD, and first and last maintenance doses, respectively. The minimum mean concentration (C(min)) increased from 100±23 ng/mL after the LD to 132±38 ng/mL at Day 7. Then, the C(min) remained constant until Day 9. The average concentration at steady state (C(avg)) was 150±45 ng/mL, which compares well to the C(avg) (130±36 ng/mL) reported after multiple daily doses at 0.1 mg/kg. The administration of the single LD allowed achievement of the average steady state drug concentrations faster than a multi-dose regimen without a loading dose. After the LD, firocoxib at 0.1 mg/kg every 24 h was able to maintain a relatively constant average drug concentration which should produce less variability in onset of action and efficacy.
University of Tennessee, Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, 2407 River Drive, Knoxville, TN 37996, USA. Electronic address: scox6@utk.edu.
S
S
Cox
N
N
Villarino
C
C
Sommardahl
V
V
Kvaternick
C
C
Zarabadipour
L
L
Siger
J
J
Yarbrough
A
A
Amicucci
K
K
Reed
D
D
Breeding
T
T
Doherty
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D013450:Sulfones / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013450:Sulfones; D015107:4-Butyrolactone; C487384:firocoxib
Firocoxib; Horse; Multi-dose regimen; Non-steroidal anti-inflammatory drug; Osteoarthritis; Pharmacokinetics