Raven Biosolutions LLC, San Carlos, CA 94070, USA.
J Ocul Pharmacol Ther. 2011 Apr;27(2):173-8. doi: 10.1089/jop.2010.0135. Epub 2011 Feb 25.
Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model.
At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)-dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC(50)) for COX isoenzymes.
Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E(2) and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E(2) elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC(50) for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC(50) for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels.
Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC-dextran leakage. The difference in inflammation suppression may be due to differences in tissue concentrations and/or greater COX-1 suppression by ketorolac 0.45%.
局部非甾体抗炎药的抗炎活性是通过抑制环氧化酶（COX）同工酶来介导的。本研究比较了兔模型中局部应用酮咯酸 0.45%和溴芬酸 0.09%眼药水的眼内通透性和抑制炎症作用。
在 0 小时，36 只兔子接受了酮咯酸 0.45%、溴芬酸 0.09%或人工泪液 3 次，每次间隔 20 分钟。每组中的一半兔子在 1 小时时接受脂多糖（LPS）和荧光素异硫氰酸酯（FITC）-葡聚糖静脉注射，另一半在 10 小时时接受注射。在前一组中，在 2 小时（峰值）和在后一组中在 11 小时（谷值）收集水样和虹膜睫状体（ICB）样本。另外一组 6 只动物仅接受 FITC-葡聚糖，1 小时后收集样本。将峰值和谷值非甾体抗炎药浓度与先前确定的 COX 同工酶的半最大抑制浓度（IC（50））进行比较。
酮咯酸的峰值和谷值水样和 ICB 浓度至少是溴芬酸的 7 倍或更高。在峰值水平时，酮咯酸 0.45%和溴芬酸 0.09%均显著抑制 LPS 诱导的水样前列腺素 E（2）和 FITC-葡聚糖升高（P<0.01）。在谷值时，两种研究药物均显著抑制 LPS 诱导的水样前列腺素 E（2）升高（P<0.05），但仅酮咯酸 0.45%显著降低 LPS 诱导的水样 FITC-葡聚糖升高（P<0.01）。水样和 ICB 中的酮咯酸浓度在峰值和谷值时均超过其对 COX-1 和 COX-2 的 IC（50）。水样和 ICB 中的溴芬酸浓度在峰值和谷值时均超过其对 COX-2 的 IC（50），但在谷值水样水平和峰值和谷值 ICB 水平时均未超过其对 COX-1 的 IC（50）。
酮咯酸 0.45%和溴芬酸 0.09%在峰值时均有效抑制炎症。在谷值时，只有酮咯酸 0.45%有效地抑制了 FITC-葡聚糖渗漏所测量的炎症。炎症抑制的差异可能是由于组织浓度的差异和/或酮咯酸 0.45%对 COX-1 的抑制作用更强。
