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Aims

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the production of prostaglandins and other inflammatory mediators by inhibiting the activity of the cyclo-oxygenase enzymes (COX). Two major isoforms of COX enzymes exist: COX-2, which is expressed during the inflammatory response, and COX-1, which is responsible for the physiological production of prostaglandin that regulates tissue homeostasis. The study aims to evaluate the effect of firocoxib ex vivo in the horse as, to the authors' knowledge, published studies assess its effect only in vitro.

Methods

Horses (n = 18) undergoing elective surgery were recruited and allocated to treatment groups depending on clinician preference (1) phenylbutazone (4.4 mg/kg bwt i.v. b.i.d.), (2) flunixin meglumine (FM, 1.1 mg/kg bwt i.v. b.i.d.) and (3) firocoxib (FIR, 0.1 mg/kg bwt i.v. s.i.d.). Residual blood samples were collected prior to NSAIDs (T0), 2 h after NSAIDs (T2), and 24 h following surgery (T24). The COX activity was measured using validated immune-enzymatic assays. A Kruskall–Wallis test was used to determine the effect of time and treatment on COX-1 and COX-2 activity. Bonferroni corrections were used to identify the level of significance accounting for multiple comparisons (P<0.017).

Results

At T2 and T24, the relative COX-1 activity was significantly greater in horses receiving firocoxib compared with horses receiving either phenylbutazone (P<0.008) or flunixin meglumine (P<0.005). At T2 and T24, COX-1 activity was reduced (compared with baseline) in horses receiving phenylbutazone or flunixin meglumine. The effect on COX-2 activity was not significantly different between drugs (P = 0.471).

Conclusions and practical significance

Cyclo-oxygenase selectivity of firocoxib is demonstrated ex vivo. Firocoxib is as effective as phenylbutazone or flunixin meglumine in modulating the production of prostaglandins by COX-2 isoenzyme, whilst the physiological action of COX-1 isoenzyme is preserved with firocoxib, but not with phenylbutazone and flunixin ex vivo.

Ethical animal research

Study approved by Ethics and Welfare Committee - School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow. Sources of funding: Funding provided by John Crawford Endowment Fund, and Mrs I.J. Gates Charity Fund, University of Glasgow. Competing interests: None.