Rate limiting barrier to the penetration of ocular hypotensive beta blockers across the corneal epithelium in the pigmented rabbit.
Rate limiting barrier to the penetration of ocular hypotensive beta blockers across the corneal epithelium in the pigmented rabbit.
复制标题
降眼压β受体阻滞剂穿过色素兔角膜上皮的限速屏障。
DOI：
10.1089/jop.1990.6.329
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Lee,VH
中科院分区：
文献类型：
--
作者：
Shih,RL;Lee,VH
本研究的目的是确定眼内分泌性β受体阻滞剂穿透有色家兔角膜上皮的限速层。研究的β受体阻滞剂按亲脂性增加的顺序为阿替洛尔、噻吗洛尔、左布诺洛尔和倍他洛尔。在改良的Ussing室中，使用离体有色兔角膜评价240分钟以上的角膜药物渗透。反相HPLC为分析方法。将角膜预暴露于20-100 μM毛地黄皂苷15 min，试图剥离角膜上皮的选择性层。角膜上皮对亲脂性很强的倍他洛尔的渗透没有抵抗力。中度亲脂性噻吗洛尔和左布诺洛尔的角膜渗透阻力主要在角膜上皮的表面细胞层。对于亲水性阿替洛尔，对角膜药物渗透的抗性似乎延伸到所有角膜上皮细胞层。上述发现表明，限制眼部给药药物角膜渗透的角膜上皮细胞层数量与药物亲脂性呈负相关。
The objective of this study was to determine the rate-limiting layer(s) in the penetration of ocular hypotensive beta blockers across the corneal epithelium in the pigmented rabbit. The beta blockers studied were, in order of increasing lipophilicity, atenolol, timolol, levobunolol, and betaxolol. Corneal drug penetration was evaluated over 240 min using the isolated pigmented rabbit cornea in the modified Ussing chamber. Reversed phase HPLC was the analytical methodology. The cornea was preexposed to 20-100 μM digitonin for 15 min in an attempt to strip off selective layers of the corneal epithelium. The corneal epithelium offered no resistance to the penetration of the very lipophilic betaxolol. The major resistance to the corneal penetration of the moderately lipophilic timolol and levobunolol was in the superficial cell layers of the corneal epithelium. For the hydrophilic atenolol, the resistance to corneal drug penetration appeared to extend across all corneal epithelial cell layers. The above findings suggest that the number of corneal epithelial cell layers limiting the corneal penetration of ocularly administered drugs is inversely related to drug lipophilicity.