Cheng Z, Nolan A M, McKellar Q A
Department of Veterinary Preclinical Studies, University of Glasgow, UK.
Inflammation. 1998 Aug;22(4):353-66. doi: 10.1023/a:1022364731126.
The anti-inflammatory effects of the non-steroidal anti-inflammatory drugs phenylbutazone (PBZ) and flunixin meglumine (FM) and the relationship between the effects and drug concentration in vivo were studied using a subcutaneous tissue-cage model in sheep. Intracaveal injection of carrageenan induced prostaglandin (PG) E2 production in tissue-cage exudate (maximal concentration, 101 nM) with significant increases in white blood cell (WBC) numbers, skin temperature over the inflamed cage and exudate leukotriene B4 (LTB4) concentration (P < 0.05). Intravenous PBZ, 4.4 mg kg-1 produced mild inhibition of exudate PGE2 generation (10%), but greater inhibition of serum TXB2 (75.3%). The IC50 for TXB2 was 36.0 microM. Phenylbutazone did not alter effects on skin temperature, WBC numbers or exudate LTB4 concentrations. Intravenous FM, 1.1 mg kg-1, significantly inhibited carrageenan-induced exudate PGE2 formation (Emax, 100%, IC50, < 0.4 nM) and serum TXB2 generation (Emax, 100%, IC50, 17 nM) for up to 32 h. Flunixin meglumine significantly inhibited the rise in skin temperature but had a limited effect on exudate WBC. Phenylbutazone and FM have distinct effects on carrageenan-induced cyclooxygenase (COX-2) and platelet COX (COX-1). Flunixin meglumine was a more potent COX inhibitor than PBZ and was more selective for the inducible form of COX in vivo.
使用绵羊皮下组织笼模型研究了非甾体抗炎药保泰松（PBZ）和氟尼辛葡甲胺（FM）的抗炎作用以及体内效应与药物浓度之间的关系。向组织笼内注射角叉菜胶可诱导组织笼渗出液中前列腺素（PG）E2生成（最大浓度为101 nM），同时白细胞（WBC）数量、发炎笼上方的皮肤温度和渗出液白三烯B4（LTB4）浓度显著增加（P < 0.05）。静脉注射4.4 mg kg-1的PBZ可轻度抑制渗出液PGE2生成（10%），但对血清TXB2的抑制作用更强（75.3%）。TXB2的IC50为36.0 microM。保泰松未改变对皮肤温度、WBC数量或渗出液LTB4浓度的影响。静脉注射1.1 mg kg-1的FM可显著抑制角叉菜胶诱导的渗出液PGE2形成（Emax，100%，IC50，< 0.4 nM）和血清TXB2生成（Emax，100%，IC50，17 nM），长达32小时。氟尼辛葡甲胺显著抑制皮肤温度升高，但对渗出液WBC的影响有限。保泰松和FM对角叉菜胶诱导的环氧化酶（COX-2）和血小板COX（COX-1）有不同的作用。氟尼辛葡甲胺是比PBZ更有效的COX抑制剂，并且在体内对诱导型COX更具选择性。
