Strøm H, Thomsen M K
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
J Vet Pharmacol Ther. 1990 Jun;13(2):186-91. doi: 10.1111/j.1365-2885.1990.tb00767.x.
Non-steroidal anti-inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated the in-vitro and ex-vivo effects of phenylbutazone and flunixin on leukotriene-B4-directed migration of canine PMN. Furthermore, in-vitro comparison was made to indomethacin and the 5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). In vitro, flunixin and NDGA were the most potent inhibitors, with IC50S of 13 and 7 mumol/l, respectively. Phenylbutazone had an IC50 of 42 mumol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 mumol/l. Ex vivo, flunixin almost completely abolished the LTB4 response at 1 h, and still possessed significant inhibitory activity 24 h after a dosage of 1 mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P less than 0.05) at 1 h following an i.v. dose of 20 mg/kg. It is suggested that part of the anti-inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.
非甾体抗炎药在抑制不同物种多形核白细胞（PMN）功能的能力上存在差异。本研究调查了保泰松和氟尼辛对犬PMN白三烯B4介导迁移的体外和体内外效应。此外，还与吲哚美辛和5-脂氧合酶抑制剂去甲二氢愈创木酸（NDGA）进行了体外比较。在体外，氟尼辛和NDGA是最有效的抑制剂，IC50分别为13和7μmol/L。保泰松的IC50为42μmol/L，而吲哚美辛在浓度低于100μmol/L时未达到50%的抑制率。在体内外，氟尼辛在静脉注射1mg/kg剂量1小时后几乎完全消除了白三烯B4反应，并且在24小时后仍具有显著的抑制活性。保泰松在体内外活性较低，但在静脉注射20mg/kg剂量1小时后确实抑制了趋化作用23%（P<0.05）。提示氟尼辛在犬体内的部分抗炎作用可能归因于对PMN募集的抑制。
