van Eyk Armorel D, Seifart Heiner I, Meyer David, van der Bijl Pieter
Division of Pharmacology, Department of Medicine, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Cornea. 2009 May;28(4):441-6. doi: 10.1097/ICO.0b013e31818c901f.
To compare the in vitro penetration of azithromycin and clarithromycin across both human and rabbit corneas.
In vitro diffusion studies were performed on frozen-thawed (liquid nitrogen, -80 degrees C) corneas using a flow-through diffusion apparatus (24 hours, 20 degrees C, 1.5 mL/h). Either phosphate-buffered saline (PBS) or 2 mg/g polyacrylic acid (Teargel) formulations of clarithromycin and azithromycin (1 or 4 mg/mL) were used in the donor chambers. Effluent samples collected (2 hours) were analyzed using binary high-performance liquid chromatography in conjunction with either UV/VIS or tandem mass spectrometry detection.
The flux values of azithromycin (PBS and polyacrylic acid) across both types of corneas showed concentration dependence. Polyacrylic acid formulations showed a decrease in flux values of azithromycin across both types of corneas. For clarithromycin, flux values across both types of corneas were approximately 2.3-2.4 times higher than azithromycin. The flux values of azithromycin at 4 mg/mL (PBS and polyacrylic acid) across human cornea were higher than those across rabbit cornea, whereas the inverse was true at 1 mg/mL PBS for both drugs.
Both macrolides penetrated the corneas, and the flux values were found to be concentration dependent (azithromycin). Clarithromycin had a higher diffusion rate across corneas than azithromycin. Although the human cornea had a higher permeability to azithromycin at a higher concentration, the inverse was found at lower concentrations for both drugs. Rabbit cornea can be used in general as an in vitro permeability model for human cornea; however, care must be taken with the extrapolation of results.
比较阿奇霉素和克拉霉素在人角膜和兔角膜中的体外渗透情况。
使用流通扩散装置（24小时，20℃，1.5 mL/h）对经冻融（液氮，-80℃）处理的角膜进行体外扩散研究。供体室中使用磷酸盐缓冲盐水（PBS）或克拉霉素和阿奇霉素（1或4 mg/mL）的2 mg/g聚丙烯酸（泪凝胶）制剂。收集流出样品（2小时），采用二元高效液相色谱结合紫外/可见或串联质谱检测进行分析。
阿奇霉素（PBS和聚丙烯酸）在两种角膜上的通量值均呈现浓度依赖性。聚丙烯酸制剂显示阿奇霉素在两种角膜上的通量值均降低。对于克拉霉素，在两种角膜上的通量值比阿奇霉素高约2.3 - 2.4倍。4 mg/mL阿奇霉素（PBS和聚丙烯酸）在人角膜上的通量值高于兔角膜，而对于两种药物，1 mg/mL PBS时情况相反。
两种大环内酯类药物均能穿透角膜，且通量值呈浓度依赖性（阿奇霉素）。克拉霉素在角膜上的扩散速率高于阿奇霉素。虽然在较高浓度时人角膜对阿奇霉素的通透性较高，但在较低浓度时两种药物情况相反。兔角膜一般可作为人角膜的体外通透性模型；然而，在结果外推时必须谨慎。
