Kojima M, Hockwin O, Sasaki K
Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan.
Lens Eye Toxic Res. 1992;9(3-4):547-58.
To investigate the route of drug penetration into the eye and drug distribution patterns in the lens, the distribution of aldose reductase inhibitor (AL-04114) in the lens was measured in short term bovine lens organ cultures and topical administration to rabbit eyes. A micro lens sectioning technique was applied to determine drug localization within the lens. Freshly enucleated bovine lenses were incubated with different concentrations of an ARI (AL-04114)-containing medium for 3 hours. For the in vivo study, 40 microliters of 0.3% AL-04114 (ophthalmic solution) were administered into the cul de sacs of rabbits 3 times at 3 hour intervals. After the incubation and final instillation, the lenses were divided into an equatorial ring and several layered sections. Drug concentration was measured by a reversed-phase HPLC system. The drug concentration was highest within the layer of the posterior shallow cortex > equator > anterior shallow cortex. No drug penetration was observed in the anterior/posterior deeper cortex or nucleus in vitro. The in vivo experiment revealed drug penetration in the equator and anterior shallow cortex, but not in any other lens layers. Drug penetration was detected within the serum and aqueous humor, but not in the vitreous.
为研究药物进入眼睛的途径以及药物在晶状体中的分布模式，在短期牛晶状体器官培养物中并通过对兔眼进行局部给药，测量了醛糖还原酶抑制剂（AL - 04114）在晶状体中的分布。应用微透镜切片技术确定药物在晶状体内的定位。将新鲜摘除的牛晶状体与不同浓度的含ARI（AL - 04114）培养基孵育3小时。对于体内研究，以3小时间隔向兔眼结膜囊内滴注3次40微升0.3%的AL - 04114（眼药水）。孵育和最后一次滴注后，将晶状体分为赤道环和若干分层切片。通过反相高效液相色谱系统测量药物浓度。药物浓度在晶状体后浅皮质层>赤道>前浅皮质层中最高。在体外，未观察到药物渗透到前/后深皮质层或核中。体内实验显示药物渗透到赤道和前浅皮质层，但未渗透到晶状体的任何其他层。在血清和房水中检测到药物渗透，但在玻璃体中未检测到。
