Waterbury L David, Flach Allan J
J Ocul Pharmacol Ther. 2006 Jun;22(3):155-9. doi: 10.1089/jop.2006.22.155.
The aim of this study was to compare the anti-inflammatory activities of ketorolac tromethamine 0.4% and 0.1%; diclofenac sodium 0.1%; and loteprednol etabonate 0.5% suspension in an animal model of ocular inflammation.
An ocular inflammatory response was induced in New Zealand White rabbits by the intravenous (i.v.) administration of 10 microg/kg lipopolysaccharide (LPS). In study animals, 1 eye was treated topically with 50 microL of study medication (n = 8 animals per drug) and the other eye was treated topically with a 50-microL vehicle (buffered saline). In control animals (n = 8), both eyes were treated with vehicle. All animals were treated twice: 2 h and 1 h before LPS challenge. The breakdown of the blood-aqueous barrier in the anterior chamber was measured by fluorophotometry (FITC-dextran 30 mg/kg, i.v. given immediately after LPS challenge). Aqueous prostaglandin E(2) (PGE(2)) levels were measured using an enzyme-linked immunosorbent assay (ELISA) immunoassay.
Ketorolac 0.4% resulted in a nearly complete inhibition of endotoxin-induced increases in FITC-dextran and PGE(2) synthesis (P < 0.001 vs. vehicle). Diclofenac 0.1% had much less of an effect on these parameters (P < 0.01 vs. ketorolac 0.4%). Loteprednol 0.5% was no more effective than vehicle at inhibiting increases in FITC-dextran.
Ketorolac has greater anti-inflammatory effects than diclofenac and loteprednol.
本研究旨在比较0.4%和0.1%的酮咯酸氨丁三醇、0.1%的双氯芬酸钠以及0.5%的氯替泼诺混悬液在眼部炎症动物模型中的抗炎活性。
通过静脉注射10微克/千克脂多糖（LPS）诱导新西兰白兔产生眼部炎症反应。在研究动物中，一只眼睛局部给予50微升研究药物（每种药物n = 8只动物），另一只眼睛局部给予50微升赋形剂（缓冲盐水）。在对照动物（n = 8）中，两只眼睛均用赋形剂治疗。所有动物均接受两次治疗：在LPS攻击前2小时和1小时。通过荧光光度法（在LPS攻击后立即静脉注射30毫克/千克异硫氰酸荧光素 - 葡聚糖）测量前房血 - 房水屏障的破坏情况。使用酶联免疫吸附测定（ELISA）免疫测定法测量房水前列腺素E2（PGE2）水平。
0.4%的酮咯酸几乎完全抑制了内毒素诱导的异硫氰酸荧光素 - 葡聚糖增加和PGE2合成（与赋形剂相比，P < 0.001）。0.1%的双氯芬酸钠对这些参数的影响要小得多（与0.4%的酮咯酸相比，P < 0.01）。0.5%的氯替泼诺在抑制异硫氰酸荧光素 - 葡聚糖增加方面并不比赋形剂更有效。
酮咯酸比双氯芬酸钠和氯替泼诺具有更强的抗炎作用。
