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Abstract

Location of penetration and metabolic barriers to levobunolol in the corneal epithelium of the pigmented rabbit.

P Ashton, W Wang and V H Lee
Journal of Pharmacology and Experimental Therapeutics November 1991, 259 (2) 719-724;
P Ashton
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W Wang
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V H Lee
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Abstract

The objective of this study was to determine which of the five or six corneal epithelial layers was rate-limiting in the corneal penetration and metabolism of levobunolol in the pigmented rabbit. Corneal penetration and metabolism were evaluated using the isolated cornea in the modified Ussing chamber. Levobunolol and its metabolite, dihydrolevobunolol, were assayed by reversed phase high-performance liquid chromatography using spectrophotometric detection. EDTA (0.1 and 0.5%) and benzalkonium chloride (0.005-0.05%) were used to disrupt the integrity of the corneal epithelial layers. EDTA, which loosened the tight junctions between the superficial corneal epithelial cells, reduced both the transcorneal flux and metabolism of levobunolol. In contrast, benzalkonium chloride, which disrupted the integrity of the outermost corneal epithelial layers, enhanced the transcorneal levobunolol flux while reducing its extent of metabolism. The extent of enhancement in transcorneal flux afforded by 0.025% benzalkonium chloride was comparable to that seen in the deepithelized cornea. Within 5 min of contact by the corneal epithelium with this preservative, the ratio of dihydrolevobunolol concentration on the endothelial to the epithelial side was reduced by two-thirds. Although direct confirmation is required, the above findings are consistent with the hypothesis that the rate-limiting layer to corneal penetration of levobunolol resides in the outermost two to three layers of the corneal epithelium, whereas the metabolic barrier resides in deeper lying regions.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 259, Issue 2
1 Nov 1991
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Abstract

Location of penetration and metabolic barriers to levobunolol in the corneal epithelium of the pigmented rabbit.

P Ashton, W Wang and V H Lee
Journal of Pharmacology and Experimental Therapeutics November 1, 1991, 259 (2) 719-724;

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Abstract

Location of penetration and metabolic barriers to levobunolol in the corneal epithelium of the pigmented rabbit.

P Ashton, W Wang and V H Lee
Journal of Pharmacology and Experimental Therapeutics November 1, 1991, 259 (2) 719-724;
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