Brideau C, Van Staden C, Chan C C
Department of Biochemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada.
Am J Vet Res. 2001 Nov;62(11):1755-60. doi: 10.2460/ajvr.2001.62.1755.
To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats.
Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats.
Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, carprofen, 5-bromo-2[4-fluorophenyl]-3-14-methylsulfonylphenyl]-thiophene (DuP 697), 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furan one (DFU), 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone (MF-tricyclic), and celecoxib. Potency of each test compound was determined by calculating the concentration that resulted in inhibition of 50% of COX activity (IC50). Selectivity was determined by calculating the ratio of IC50 for COX-1 to IC50 for COX-2 (COX-1/COX-2 ratio).
The novel compound DFU was the most selective COX-2 inhibitor in equine, canine, and feline blood; COX-1/COX-2 ratios were 775, 74, and 69, respectively. Carprofen was the weakest inhibitor of COX-2, compared with the other COX-2 selective inhibitors, and did not inhibit COX-2 activity in equine blood. In contrast, NSAID such as phenylbutazone and flunixin meglumine were more potent inhibitors of COX-1 than COX-2 in canine and equine blood.
The novel COX-2 inhibitor DFU was more potent and selective in canine, equine, and feline blood, compared with phenylbutazone, flunixin meglumine, and carprofen. Compounds that specifically inhibit COX-2 may result in a lower incidence of adverse effects, compared with NSAID, when administered at therapeutic dosages to horses, dogs, and cats.
测定非甾体抗炎药（NSAID）和环氧化酶（COX）特异性抑制剂对马、犬和猫全血中环氧化酶活性的作用强度及选择性。
30匹健康马、48只健康犬和9只健康猫的血液样本。
分别通过测量添加和不添加不同浓度的苯基丁氮酮、氟尼辛葡甲胺、酮洛芬、双氯芬酸、吲哚美辛、美洛昔康、卡洛芬、5-溴-2-[4-氟苯基]-3-[4-甲基磺酰基苯基]-噻吩（DuP 697）、5,5-二甲基-3-(3-氟苯基)-4-(4-甲基磺酰基)苯基-2(5H)-呋喃酮（DFU）、3-(3,4-二氟苯基)-4-(4-(甲基磺酰基)苯基)-2-(5H)-呋喃酮（MF-三环化合物）和塞来昔布的全血中凝血诱导的血栓素和脂多糖诱导的前列腺素E2浓度，来测定COX-1和COX-2的活性。通过计算导致COX活性抑制50%的浓度（IC50）来确定每种受试化合物的作用强度。通过计算COX-1的IC50与COX-2的IC50之比（COX-1/COX-2比率）来确定选择性。
新型化合物DFU是马、犬和猫血液中最具选择性的COX-2抑制剂；COX-1/COX-2比率分别为775、74和69。与其他COX-2选择性抑制剂相比，卡洛芬是最弱的COX-2抑制剂，且在马血中不抑制COX-2活性。相比之下，在犬和马的血液中，苯基丁氮酮和氟尼辛葡甲胺等NSAID对COX-1的抑制作用比对COX-2更强。
与苯基丁氮酮、氟尼辛葡甲胺和卡洛芬相比，新型COX-2抑制剂DFU在犬、马和猫血液中的作用更强且更具选择性。当以治疗剂量给马、犬和猫用药时，与NSAID相比，特异性抑制COX-2的化合物可能导致更低的不良反应发生率。
Zotero 插件