Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability.
Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability.
复制标题
兔角膜中酯酶的分布及其对眼部药物生物利用度的影响。
DOI：
10.1002/bdd.2510030402
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发表时间：
1982
影响因子：
2.1
通讯作者：
StratfordJr,RE
中科院分区：
文献类型：
--
作者：
Lee,VH;Morimoto,KW;StratfordJr,RE
角膜是眼科外用药物进入眼部的主要途径，通过抵抗药物渗透和在渗透过程中代谢药物来控制最终吸收的活性药物的量。这项研究试图测定角膜及其两个成分层--上皮和基质--内皮细胞中的酯酶活性，以预测含有酯键的药物在运输过程中代谢的程度。这是通过将不同年龄组的白化兔和有色兔的角膜匀浆与模型底物α-乙酸萘酯孵育，并监测α-萘酚随时间的变化而产生的荧光强度来实现的。结果表明：(1)角膜上皮酯酶活性约为基质-内皮的两倍；(2)完整角膜的酯酶活性与角膜上皮和基质-内皮的活性呈线性相关；(3)角膜及其组成层的酯酶活性随年龄和应变而变化。根据这些结果，预计大部分酯酶介导的水解会发生在上皮细胞中，因此药物在该组织中的停留时间可以对其眼部生物利用度产生重大影响。
Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers— epithelium and stroma‐endothelium—so as to anticipate the extent to which drugs containing ester linkages will be metabolized during transport. This has been achieved by incubating corneal homogenates of albino and pigmented rabbits of various age groups with α‐naphthyl acetate, the model substrate, and monitoring the fluorescence intensity due to α‐naphthol as a function of time. The results indicate that: (1) esterase activity in the epithelium is approximately twice that in the stroma‐endothelium; (2) esterase activity in the intact cornea is linearly related to those in the epithelium and the stroma‐endothelium; and (3) the esterase activity in the cornea and its component layers varies with rabbit's age and strain. According to these results the bulk of esterase‐mediated hydrolysis is expected to take place in the epithelium, so that the residence time of a drug in this tissue can have a significant impact on its ocular bioavailability.