Brechue W F, Maren T H
University of Florida Health Science Center, Department of Pharmacology and Therapeutics, Gainesville 32610.
Invest Ophthalmol Vis Sci. 1993 Jul;34(8):2581-7.
To evaluate the effect of drug ionization on the ocular hypotensive activity of topical carbonic anhydrase inhibitors.
Ocular normotensive New Zealand albino and ocular hypertensive Dutch Belted pigmented rabbits were used. Tonometric intraocular pressure levels were taken after topical application of 50 microliters of drug (at various concentrations and pH values) to one eye with the contralateral eye used as an untreated control. The drugs tested were MK-927, L-662,583, and AHR-16329. Eye tissues were analyzed for drug by our enzymatic methods.
In all cases, the more ionized the applied drug the greater the ocular hypotensive activity. Tissue distribution studies showed that there was more drug found in the eye after the ionized form of a drug was applied than that found after application of the less ionized forms.
Increasing the ionization of three ampholyte topical carbonic anhydrase inhibitors increases their ocular hypotensive activity. These data taken with ocular disposition data suggest that ionized compounds of this type are more readily sequestered in the cornea, which serves as a drug depot for prolonged drug delivery and activity.
评估药物离子化对局部碳酸酐酶抑制剂眼降压活性的影响。
使用眼压正常的新西兰白化兔和眼压高的荷兰带色素兔。在一只眼睛局部应用50微升药物（不同浓度和pH值）后测量眼压水平，对侧眼睛作为未治疗对照。所测试的药物为MK - 927、L - 662,583和AHR - 16329。通过我们的酶法分析眼组织中的药物。
在所有情况下，应用的药物离子化程度越高，眼降压活性越大。组织分布研究表明，应用药物的离子化形式后，眼中发现的药物比应用较少离子化形式后发现的更多。
增加三种两性电解质局部碳酸酐酶抑制剂的离子化程度可提高其眼降压活性。这些数据与眼内处置数据表明，这类离子化化合物更容易在角膜中蓄积，角膜可作为药物储存库实现药物的长效递送和活性。
