AJVR, Vol 66, No. 8, August 2005 1441 R eportedly, pharmacokinetic parameters and drug metabolism differ considerably among breeds of dogs. 1-3 Greyhounds metabolize cyclizine (a histamine receptor 1 antagonist) differently than other breeds of dogs or species. 4,5 Barbiturates have also been reported to have different pharmacokinetics in Greyhounds, compared with other breeds of dogs. 6,7 The plasma clearance of pentobarbital and methohexital is slower in Greyhounds than mixed-breed dogs with a corre- sponding increase in mean residence time. 6 Propofol hydroxylase activity is 3-fold lower in Greyhounds than in Beagles. 8,9 Because of selective breeding over several centuries, it is possible that differences in renal or hepatic physiology have developed in Greyhounds, leading to differences in xenobiotic distribution, metabolism, and excretion, compared with other breeds of dogs. Numerous factors lead to modifications in the pharmacokinetics of a pharmaceutical compound. These factors include differences in cytochrome P-450 isoform expression, renal and hepatic physiology, p-glycoprotein expression, and gastrointestinal physi- ology. 8,10-14 Differences in absorption, distribution, metabolism, or elimination can, and often do, make extrapolation from 1 species to another difficult. Presently, Greyhounds are treated with various nonsteroidal anti-inflammatory drugs (NSAIDs), which are not specific cyclooxygenase inhibitors, despite the fact that these drugs can have serious adverse effects, even when used at the labeled dose. 15,16 Celecoxib may be an alternative treatment for inflam- mation in racing greyhounds. Celecoxib is metabolized in humans by cytochrome P-450 2C9 and in Beagles by cytochrome P-450 2D15 to hydroxy-celecoxib and car- boxyl-celecoxib, then subsequent noncytochrome P- 450 mediated phase II glucuronide conjugation of car- boxyl-celecoxib occurs. 2,17 Metabolites are excreted in urine and feces; however, excretion in feces is the pre- dominate route. 18 Two distinct phenotypes have been detected in laboratory-raised Beagles and humans, those that metabolize celecoxib extensively and those that metabolize celecoxib poorly. 2,17,19 Received April 6, 2004. Accepted November 2, 2004. From the Departments of Anatomy and Physiology (Hunter, Koch, Pellerin, Halstead) and Clinical Sciences (Radlinsky, Corse), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506. Dr. Hunter’s present address is Elanco Animal Health, 2001 W Main St, PO Box 708, Greenfield, IN 46140. Dr. Radlinsky’s present address is the Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602. Dr. Corse’s present address is Northlake Veterinary Specialists, 935 Montreal Rd, Clarkston, GA 30021. Funded by a grant from the Kansas Racing and Gaming Commission. Presented in part at the 21st Annual American College of Veterinary Internal Medicine Forum, Charlotte, NC, June 2003. Address correspondence to Dr. Hunter. Plasma pharmacokinetics and synovial fluid concentrations after oral administration of single and multiple doses of celecoxib in Greyhounds Robert P. Hunter, PhD; MaryAnn Radlinsky, DVM, MS; David E. Koch, MS; Matthew Corse, DVM; Marie A. Pellerin, BA; Jennifer Halstead, BS Objective⎯To determine the plasma pharmacokinet- ics and synovial fluid concentrations after oral admin- istration of single and multiple doses of celecoxib in Greyhounds. Animals⎯7 adult Greyhounds. Procedures⎯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 admin- istered. 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 cele- coxib resulted in a significant decrease (40%) in medi- an area under the curve (AUC) values and a corre- sponding decrease in median maximum concentra- tions (C max ; 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 dis- tributes into the synovial fluid of Greyhounds. Although the exact mechanism for the decreases in AUC and C max is not known, results suggested that the plasma pharmacokinetics of celecoxib are differ- ent after administration of multiple doses in Greyhounds. These findings warrant further investiga- tion on the absorption, distribution, metabolism, and elimination of celecoxib in Greyhounds and other breeds of dogs. (Am J Vet Res 2005;66:1441–1445)