Shih R L, Lee V H
University of Southern California, School of Pharmacy, Los Angeles.
J Ocul Pharmacol. 1990 Winter;6(4):329-36. doi: 10.1089/jop.1990.6.329.
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 microM 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.
本研究的目的是确定色素兔眼中降眼压β受体阻滞剂穿透角膜上皮的限速层。所研究的β受体阻滞剂按亲脂性递增顺序依次为阿替洛尔、噻吗洛尔、左布诺洛尔和倍他洛尔。使用改良的Ussing室中的离体色素兔角膜，在240分钟内评估角膜药物渗透性。反相高效液相色谱法为分析方法。为了剥离角膜上皮的选择性层，将角膜预先暴露于20 - 100微摩尔的洋地黄皂苷中15分钟。角膜上皮对亲脂性很强的倍他洛尔的渗透没有阻力。中度亲脂性的噻吗洛尔和左布诺洛尔角膜渗透的主要阻力在于角膜上皮的表层细胞层。对于亲水性的阿替洛尔，角膜药物渗透的阻力似乎延伸至所有角膜上皮细胞层。上述发现表明，限制眼用药物角膜渗透的角膜上皮细胞层数与药物亲脂性呈负相关。
