Conroy C W, Maren T H
University of Florida College of Medicine, Department of Pharmacology and Therapeutics, Gainesville 32610, USA.
J Ocul Pharmacol Ther. 1998 Dec;14(6):565-73. doi: 10.1089/jop.1998.14.565.
The accession of methazolamide in ionized and unionized form to cornea, sclera, aqueous humor and ciliary process was studied 10 minutes following separate application to either sclera or cornea of a 1 mM solution. Cornea and ciliary process concentrations were 27.3 and 14.5 microM for unionized application to cornea and 10.1 and 7.1 microM for ionized application. Bulk aqueous humor concentrations were much lower, 3.1 and 1.1 microM, and cannot account for drug found in ciliary process on this time scale. Scleral application of drug, by contrast, gave undetectable ciliary process concentrations. These results are presented as a model for drug disposition following single drop topical sulfonamide therapy. The scleral pathway for drug delivery to ciliary process was further tested by application to sclera of 300 microL of either a 1 mM ionized or unionized solution for 30 minutes or as a 2% (85.5 mM) ionized solution for 30 minutes. In these series, red cell carbonic anhydrase was presaturated at -24 hours with drug to remove a possible route for loss of drug from sclera, that of the systemic circulation and the high concentration of carbonic anhydrase in red cells. After either ionized or unionized application, approximately 1 microM was detected in ciliary process, but all drug was attributable to the blood content of the tissue and the drug bound to red cell carbonic anhydrase. After 2% dosing, 4 microM was detected in ciliary process after allowance for drug in red cells. This concentration is below that necessary for inhibition of ciliary process carbonic anhydrase, suggesting that especially with regard to topical sulfonamide therapy, the corneal route of drug delivery to ciliary process predominates greatly over the scleral route.
在将1 mM溶液分别应用于巩膜或角膜10分钟后，研究了离子化和非离子化形式的甲醋唑胺在角膜、巩膜、房水和睫状体中的摄取情况。非离子化形式应用于角膜时，角膜和睫状体浓度分别为27.3和14.5 microM；离子化形式应用时，浓度分别为10.1和7.1 microM。房水总体浓度要低得多，为3.1和1.1 microM，在这个时间尺度上无法解释睫状体中发现的药物。相比之下，药物应用于巩膜时，睫状体浓度检测不到。这些结果作为单次滴眼局部磺胺治疗后药物处置的模型呈现。通过将300微升1 mM离子化或非离子化溶液应用于巩膜30分钟或2%（85.5 mM）离子化溶液应用于巩膜30分钟，进一步测试了药物经巩膜途径递送至睫状体的情况。在这些系列中，红细胞碳酸酐酶在 -24小时用药物预饱和，以消除药物从巩膜流失的可能途径，即体循环途径以及红细胞中高浓度碳酸酐酶的途径。离子化或非离子化应用后，在睫状体中检测到约1 microM，但所有药物都归因于组织的血液含量以及与红细胞碳酸酐酶结合的药物。2%给药后，扣除红细胞中的药物后，在睫状体中检测到4 microM。该浓度低于抑制睫状体碳酸酐酶所需的浓度，这表明特别是对于局部磺胺治疗，药物经角膜途径递送至睫状体的情况比经巩膜途径占主导得多。
