Palmero M, Bellot J L, Alcoriza N, García-Cabanes C, Orts A
Department of Interuniversitary Optics, University of Alicante, Spain.
Ophthalmic Res. 1999;31(4):309-16. doi: 10.1159/000055552.
The ocular pharmacokinetics of topical diclofenac sodium was studied in two experimental models of ocular inflammation and compared to physiological conditions. Keratitis or uveitis were induced by intrastromal injection of clove oil or by intravitreal lipopolysaccharide in rabbits. The control eyes were not inflamed. Simultaneously to the induction of inflammation, 30 microl of 0.1% diclofenac were applied topically in the right eye. Diclofenac levels were measured by HPLC in the cornea, aqueous humor (AH), iris/ciliary body (ICB) and plasma 30 min, 1, 3, 6 and 12 h after application. In physiological conditions, diclofenac reached a peak level in the cornea and ICB at 30 min slowly decreasing afterwards. Low levels of diclofenac were found in AH. In keratitic eyes, two peak levels which were significantly higher than in the controls were found in the cornea 30 min and 3 h after application. Diclofenac concentrations in keratitic AH and ICB were lower than in controls. In uveitic eyes, corneal and ICB levels peaked at 30 min, being significantly higher than in controls, and decreased quickly to very low levels at 1 h after application. In uveitic AH, diclofenac levels were lower than in controls. Plasma levels were very low (less than 0.1 microg/ml) in all experimental groups. It is concluded that the ocular pharmacokinetics of topical diclofenac is affected by inflammatory processes in the eye, reaching higher levels in the target tissues.
在两种眼部炎症实验模型中研究了局部应用双氯芬酸钠的眼部药代动力学，并与生理状况进行了比较。通过在兔角膜基质内注射丁香油或玻璃体内注射脂多糖诱导角膜炎或葡萄膜炎。对照眼未发炎。在诱导炎症的同时，将30微升0.1%的双氯芬酸局部应用于右眼。在给药后30分钟、1小时、3小时、6小时和12小时，通过高效液相色谱法测量角膜、房水（AH）、虹膜/睫状体（ICB）和血浆中的双氯芬酸水平。在生理状况下，双氯芬酸在30分钟时在角膜和ICB中达到峰值水平，随后缓慢下降。在AH中发现双氯芬酸水平较低。在角膜炎眼中，给药后30分钟和3小时在角膜中发现两个峰值水平，显著高于对照组。角膜炎性AH和ICB中的双氯芬酸浓度低于对照组。在葡萄膜炎眼中,角膜和ICB水平在30分钟时达到峰值，显著高于对照组，并在给药后1小时迅速降至非常低的水平。在葡萄膜炎性AH中，双氯芬酸水平低于对照组。所有实验组的血浆水平都非常低（低于0.1微克/毫升）。结论是，局部应用双氯芬酸的眼部药代动力学受眼部炎症过程影响，在靶组织中达到更高水平。
