Sieg J W, Robinson J R
J Pharm Sci. 1976 Dec;65(12):1816-22. doi: 10.1002/jps.2600651230.
The mechanism of corneal pilocarpine penetration was studied in the albino rabbit using radiochemical techniques. The apparent rate and extent of pilocarpine accumulation in the aqueous humor and the various cell layers of the cornea were determined for both intact and abraded eyes. For the first time, drug levels were monitored in the epithelium and stroma-endothelium of the intact cornea using a tissue-scraping technique. In addition, a new postinstillation rinsing method was devised to evaluate the rate of corneal uptake. The results demonstrate a dual role for the corneal epithelium, both as a barrier to drug penetration and as a reservoir for drug in the intact cornea. The transcorneal pilocarpine flux is slower than the data appear to indicate, and previous overestimates of the apparent absorption rate constant are due to parallel elimination processes occurring at the absorption site. Pharmacokinetic parameters were determined for each tissue to generate an overall mechanism for corneal permeation.
采用放射化学技术，在白化兔中研究了毛果芸香碱的角膜渗透机制。测定了完整眼和磨损眼房水中毛果芸香碱的表观蓄积速率和程度，以及角膜各细胞层中毛果芸香碱的表观蓄积速率和程度。首次采用组织刮取技术监测完整角膜上皮和基质-内皮中的药物水平。此外，还设计了一种新的滴药后冲洗方法来评估角膜摄取速率。结果表明，角膜上皮在完整角膜中既作为药物渗透的屏障，又作为药物的储存库，发挥双重作用。经角膜的毛果芸香碱通量比数据显示的要慢，之前对表观吸收速率常数的高估是由于吸收部位同时发生的消除过程所致。确定了每个组织的药代动力学参数，以生成角膜渗透的总体机制。
