Ex vivo COX‐1 and COX‐2 inhibition in equine blood by phenylbutazone, flunixin meglumine, meloxicam and firocoxib: Informing clinical NSAID selection

Abstract

Summary Newer cyclo‐oxygenase‐2 (COX‐2) selective nonsteroidal anti‐inflammatory drugs (NSAIDs), such as firocoxib, are proposed to reduce inhibition of cyclo‐oxygenase‐1 (COX‐1) and avoid undesirable side effects, while continuing to inhibit inflammation associated with COX‐2. However, COX selectivity is typically based on in vitro testing, which may not provide sufficient information critical for treatment selection. This study investigated the pharmacokinetics and ex vivo COX‐1 and COX‐2 inhibition of phenylbutazone, flunixin meglumine, meloxicam and firocoxib. Horses (n = 3) were administered one of the four drugs, in a randomised cross‐over design, with 3‐week washout periods. For each drug, three doses were given and sampling performed. Drug plasma concentrations, thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were determined. After one dose, TXB2 and PGE2 levels were significantly higher in horses administered firocoxib compared to flunixin meglumine. Following the third dose, TXB2 levels in horses administered firocoxib and meloxicam were significantly higher compared to flunixin meglumine or phenylbutazone; all drugs reduced PGE2 to a similar degree. The mean plasma half‐lives were 5.97 ± 0.47, 4.74 ± 0.14, 8.24 ± 3.74 and 47.42 ± 7.41 h for phenylbutazone, flunixin meglumine, meloxicam and firocoxib, respectively. Firocoxib and meloxicam exhibited significantly less COX‐1 inhibition compared to flunixin meglumine and phenylbutazone; all drugs inhibited COX‐2. The plasma half‐life of firocoxib was longer than the other NSAIDs, including meloxicam. Data from this study have important clinical relevance and should be used to inform practitioners’ drug selection of a COX‐1 sparing or traditional NSAID and dose selection and to provide knowledge of the duration for the four NSAIDs studied.

Comparison of Flunixin Meglumine, Meloxicam and Ketoprofen on Mild Visceral Post-Operative Pain in Horses

“…While the onset of the anti-inflammatory action of flunixin is within 2 h, with a peak response between 12 and 16 h and a duration of action of 36 h, ketoprofen reaches a peak response 4 h after administration and lasts for 24 h [ 22 ]. Other studies have described a more rapid and longer effect of flunixin than ketoprofen, while PK/PD of flunixin, meloxicam and phenylbutazone were similar [ 22 , 28 , 30 , 31 , 32 ]. In addition, ketoprofen was suggested to have altered plasma pharmacokinetics in the face of inflammation in peripheral compartments [ 33 , 34 , 35 ].…”

“…These findings are in agreement with a recent study evaluating the analgesic effect of these drugs following scrotal castration and supports the fact that meloxicam significantly reduces post-surgical pain and inflammation in horses following castration [ 27 ]. Equivalent levels of COX-2 inhibition were found between COX-2-selective (meloxicam or firocoxib) and nonselective (flunixin, phenylbutazone) anti-inflammatories, supporting a similar analgesic efficacy for meloxicam, firocoxib, phenylbutazone and flunixin [ 28 ].…”

Fetal Congenital Diaphragmatic Hernia and Hydramnios in a Quarter Horse Mare

“…A commercial abdominal support bandage was applied, and the wrap was tightened daily as the ventral edema and swelling decreased over time. On day 316 of gestation, NSAID therapy was changed to firocoxib (loading dose 0.3 mg/kg per os SID, then 0.1 mg/kg per os SID) [15]. Further ultrasonographic examination (US) checks were performed every 5 days, until delivery.…”

Preliminary evaluation of hepatitis A virus cell receptor 1/kidney injury molecule 1 in healthy horses treated with phenylbutazone

“…2,[8][9][10][11] Nonsteroidal anti-inflammatory drugs increase the risk of AKI by inhibiting renal vasodilatory prostaglandins, which maintain renal blood flow under conditions of renal hypoperfusion and vasoconstriction. 12,13 Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug in horses, commonly administered in the management of musculoskeletal disorders. 13 Renal papillary necrosis caused by PBZ administration has been documented in horses.…”