Evaluation of selective inhibition of canine cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory drugs

Am J Vet Res. 1998 Nov;59(11):1441-6.

Abstract

Objective: To evaluate the activity of carprofen and other nonsteroidal anti-inflammatory drugs (NSAID) against isozymes of canine cyclooxygenases (COX1 and COX2).

Procedure: Constitutive COX1 was obtained from washed canine platelets, and COX2 was obtained from a canine macrophage-like cell line that was induced with endotoxin. Activity of carprofen and other NSAID against COX1 and COX2 was compared. Dose-response curves were plotted, and calculations were performed to identify concentrations that caused 50% inhibition (IC50 [microM]) for each isozyme. Ratio of the COX1-to-COX2 IC50 was used as a measure of isozyme selectivity.

Results: Of the compounds evaluated, carprofen had the greatest selectivity for COX2. Potency of carprofen for canine COX2 was more than 100-fold greater than for canine COX1. Inhibition of canine COX2 (IC50, 0.102 microM) for the racemic mixture of carprofen (S and R stereoisomers) was primarily attributable to the S enantiomer (IC50, 0.0371 microM), which was approximately 200-fold more potent than the R enantiomer (IC50, 5.97 microM). Nimesulide had the next highest selectivity for COX2 (38-fold), and tolfenamic acid and meclofenamic acid had 15-fold selectivity for COX2. The other compounds tested did not have substantial selectivity for canine COX2 or were more selective for canine COX1.

Conclusions: Carprofen was found to be a potent inhibitor of canine COX2. Of the compounds tested, carprofen had the highest selectivity for canine COX2.

Clinical relevance: The selectivity of carprofen for canine COX2 may be an important factor for its use in dogs.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology
  • Calcimycin / pharmacology
  • Carbazoles / pharmacology*
  • Cell Line
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dogs / blood*
  • In Vitro Techniques
  • Ionophores / pharmacology
  • Isoenzymes / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Thromboxane B2 / analysis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbazoles
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Ionophores
  • Isoenzymes
  • Calcimycin
  • Thromboxane B2
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • carprofen