Objective—To determine the plasma pharmacokinetics
and synovial fluid concentrations after oral administration
of single and multiple doses of celecoxib in
Animals—7 adult Greyhounds.
Procedure—Dogs received celecoxib (median
dose, 11.8 mg/kg [range, 11.5 to 13.6 mg/kg], PO,
q 24 h) for 10 days. Blood samples were collected
prior to administration of celecoxib and serially for
24 hours after the 1st and 10th doses were administered.
A synovial joint catheter was placed into a
stifle joint in each dog for collection of synovial fluid
samples. Concentrations of celecoxib in plasma and
synovial fluid were quantified by use of a validated
liquid chromatography/mass spectrometry method.
Identification of hydroxy- and carboxyl-celecoxib in
plasma and synovial fluid was also performed.
Pharmacokinetic parameters were determined by
use of noncompartmental analysis.
Results—Administration of multiple doses of celecoxib
resulted in a significant decrease (40%) in median
area under the curve (AUC) values and a corresponding
decrease in median maximum concentrations
(Cmax; 2,620 to 2,032 ng/mL) between the 1st
and 10th doses. Synovial fluid concentrations were
less than the corresponding plasma concentrations at
all times except 24 hours after administration of the
10th dose of celecoxib.
Conclusions and Clinical Relevance—Celecoxib distributes
into the synovial fluid of Greyhounds.
Although the exact mechanism for the decreases in
AUC and Cmax is not known, results suggested that
the plasma pharmacokinetics of celecoxib are different
after administration of multiple doses in
Greyhounds. These findings warrant further investigation
on the absorption, distribution, metabolism, and
elimination of celecoxib in Greyhounds and other
breeds of dogs. (Am J Vet Res 2005;66:1441–1445)