Advertisement

Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood

Heather K. StreppaDepartment of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
Veterinary Teaching Hospital 379 East Campus Dr. University of Missouri, Columbia, MO 65211.

Search for other papers by Heather K. Streppa in
Current site
Google Scholar
PubMed
Close
 DVM
,
Chris J. JonesDepartment of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
1111 W Loop S, Suite 140 Houston, TX 77027.

Search for other papers by Chris J. Jones in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Steven C. BudsbergDepartment of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

Search for other papers by Steven C. Budsberg in
Current site
Google Scholar
PubMed
Close
 DVM, MS

Abstract

Objective—To evaluate cyclooxygenase (COX) selectivity of several nonsteroidal anti-inflammatory drugs (NSAID) in canine blood in vitro.

Animals—11 healthy adult male hound crosses.

Procedure—9 NSAID were studied at 5 concentrations. Thromboxane B2 (TxB2) was assayed as a measure of COX-1 activity in clotted blood. Prostaglandin E2 (PGE2) was assayed as a measure of COX-2 activity in heparinized, lipopolysaccharide (LPS)-stimulated blood. All assays were competitive ELISA tests. Cyclooxygenase selectivity was expressed as a ratio of the concentration of an NSAID that inhibited 50% of the activity (IC50) of COX-1 to the IC50 of COX-2. A separate ratio of the concentration that inhibited 80% of COX activity (IC80) was also determined. A ratio of < 1.0 indicated selectivity for COX-1, whereas a ratio of > 1.0 indicated COX-2 selectivity.

Results—Ketoprofen, aspirin, and etodolac were COX-1 selective. Piroxicam, meloxicam, and carprofen had COX-2 selectivity. The IC50 and IC80 values were similar for most NSAID.

Conclusion and Clinical Relevance—This methodology provides repeatable data from individual dogs and is comparable to results of previous in vitro and ex vivo models. Findings are also consistent with those of canine studies performed in vivo, suggesting that this is a viable in vitro assessment of the COX selectivity of NSAID in dogs. (Am J Vet Res 2002;63:91–94)

Abstract

Objective—To evaluate cyclooxygenase (COX) selectivity of several nonsteroidal anti-inflammatory drugs (NSAID) in canine blood in vitro.

Animals—11 healthy adult male hound crosses.

Procedure—9 NSAID were studied at 5 concentrations. Thromboxane B2 (TxB2) was assayed as a measure of COX-1 activity in clotted blood. Prostaglandin E2 (PGE2) was assayed as a measure of COX-2 activity in heparinized, lipopolysaccharide (LPS)-stimulated blood. All assays were competitive ELISA tests. Cyclooxygenase selectivity was expressed as a ratio of the concentration of an NSAID that inhibited 50% of the activity (IC50) of COX-1 to the IC50 of COX-2. A separate ratio of the concentration that inhibited 80% of COX activity (IC80) was also determined. A ratio of < 1.0 indicated selectivity for COX-1, whereas a ratio of > 1.0 indicated COX-2 selectivity.

Results—Ketoprofen, aspirin, and etodolac were COX-1 selective. Piroxicam, meloxicam, and carprofen had COX-2 selectivity. The IC50 and IC80 values were similar for most NSAID.

Conclusion and Clinical Relevance—This methodology provides repeatable data from individual dogs and is comparable to results of previous in vitro and ex vivo models. Findings are also consistent with those of canine studies performed in vivo, suggesting that this is a viable in vitro assessment of the COX selectivity of NSAID in dogs. (Am J Vet Res 2002;63:91–94)