In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats
In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats
复制标题
DOI：
10.2460/ajvr.2001.62.1755
复制
发表时间：
2001-11-01
影响因子：
1
通讯作者：
Chan, CC
中科院分区：
文献类型：
--
作者：
Brideau, C;Van Staden, C;Chan, CC
样品-测定来自马、狗和猫的全血中非甾体抗炎药（NSAID）和环氧化酶-（考克斯-）特异性抑制剂的效力和选择性。方法-通过测量凝血诱导的血栓素B-2和脂多糖诱导的前列腺素E-2来测定考克斯-1和考克斯-2的活性。在加入和不加入不同浓度保泰松、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-甲磺酰基苯基]-噻吩（DuP 697）、5，5-二甲基-3-噻吩（DuP 697）的情况下，全血中的浓度分别为2个。（3-氟苯基）-4-（4-甲基磺酰基）苯基-2（5 H）-呋喃酮（DFU）、3-（3，4-二氟苯基）-4-（4-（甲基磺酰基）苯基）-2-（5 H）-呋喃酮（MF-三环）和塞来昔布。通过计算导致抑制50%考克斯活性的浓度（IC 50）来确定每种测试化合物的效力。通过计算考克斯-1的IC 50与考克斯-2的IC 50的比率来确定选择性（考克斯-1/考克斯-2比率）.结果-新化合物DFU是马、犬和猫血液中最具选择性的考克斯-2抑制剂;考克斯-1/考克斯-2比值分别为77.5、74和69。与其他考克斯-2选择性抑制剂相比，卡洛芬是最弱的考克斯-2抑制剂，并且在马血液中不抑制考克斯-2活性。相反，NSAID如保泰松和氟尼辛葡甲胺在犬和马血液中是比考克斯-2更有效的考克斯-1抑制剂。结论和临床相关性-新型考克斯-2抑制剂DFU在犬、马和猫血液中更有效和选择性更高，与保泰松、氟尼辛葡甲胺和卡洛芬相比。当以治疗剂量给予马、犬和猫时，与NSAID相比，特异性抑制考克斯-2的化合物可能导致不良反应的发生率较低。
Objective-To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclcoxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats.Sample Population-Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats.Procedure-Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane B-2 and lipopolysaccharide-induced prostaglandin E-2 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-[4-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).Results-The novel compound DFU was the most selective COX-2 inhibitor in equine, canine, and feline blood; COX-1/COX-2 ratios were 77.5, 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.Conclusions and Clinical Relevance-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.