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.

中文翻译：

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苯丁氮酮，氟尼辛葡甲胺，美洛昔康和费洛昔布对马血中离体COX-1和COX-2的抑制作用：通知临床NSAID选择

提议使用较新的环氧合酶2（COX-2）选择性非甾体抗炎药（如非洛昔布），以减少对环氧合酶1（COX-1）的抑制并避免不良副作用，同时继续抑制与COX-2相关的炎症。但是，COX选择性通常基于体外测试，这可能无法提供足够的信息以选择治疗方法。这项研究调查了药物动力学以及离体对异丁苯酮，氟尼辛葡甲胺，美洛昔康和非洛昔布的COX-1和COX-2的抑制作用。对马（n = 3）进行随机交叉设计，给予4种药物中的1种，冲洗期为3周。对于每种药物，给予三剂并进行采样。药物血浆浓度，血栓烷B测定₂（TXB ₂）和前列腺素E ₂（PGE ₂）。一剂后，与氟尼辛葡甲胺相比，给予氟罗昔布的马的TXB ₂和PGE ₂水平明显更高。第三次给药后，与氟尼辛葡甲胺或苯基丁氮酮相比，给予氟罗昔布和美洛昔康的马匹中TXB _2的水平显着升高。所有药物降低PGE ₂达到相似的程度。苯基丁a，氟尼辛葡甲胺，美洛昔康和氟罗昔布的平均血浆半衰期分别为5.97±0.47、4.74±0.14、8.24±3.74和47.42±7.41 h。与氟尼辛葡甲胺和苯丁氮酮相比，非诺昔布和美洛昔康对COX-1的抑制作用要低得多。所有药物均抑制COX-2。氟罗昔布的血浆半衰期比其他非甾体抗炎药（包括美洛昔康）更长。这项研究的数据具有重要的临床意义，应用于告知从业者选择COX-1或传统NSAID的药物选择和剂量选择，并提供所研究的四种NSAID持续时间的知识。