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局部治疗中的药物储库

Drug reservoirs in topical therapy.

作者信息

Mindel J S, Smith H, Jacobs M, Kharlamb A B, Friedman A H

出版信息

Invest Ophthalmol Vis Sci. 1984 Mar;25(3):346-50.

PMID:6698752
Abstract

The nictitating membrane, corneal epithelium, and corneal stroma were investigated as drug reservoirs. A hydrophilic drug, D,L-epinephrine HCl, or a lipophilic drug, chloramphenicol, was applied topically to rabbit eyes. Tissue levels of radioactive drug-plus-metabolites and unmetabolized epinephrine were assayed up to 24 hrs later. On a per-mg-tissue basis, concentrations of epinephrine-plus-metabolites in the stroma-endothelium were similar to or higher than those in the epithelium. The percentages of radioactivity representing unmetabolized epinephrine in the stroma-endothelium were found to be similar to or higher than those in the epithelium. On a per-mg-tissue basis, concentrations of chloramphenicol-plus-metabolites were significantly higher in the epithelium than in the stroma-endothelium during the first 130 min after drug application. While the physical properties of these drugs determined whether a higher concentration was found in the epithelium or stroma-endothelium, the ninefold greater mass of the stroma-endothelium made it the major drug reservoir on a per-whole-tissue basis. The presence or absence of a nictitating membrane had little effect on the level of either drug in the epithelium, stromal-endothelium, or aqueous humor.

摘要

研究了瞬膜、角膜上皮和角膜基质作为药物储存库的情况。将亲水性药物盐酸D,L-肾上腺素或亲脂性药物氯霉素局部应用于兔眼。在24小时内检测放射性药物加代谢物和未代谢肾上腺素的组织水平。以每毫克组织计算,基质-内皮中肾上腺素加代谢物的浓度与上皮中的浓度相似或更高。发现基质-内皮中代表未代谢肾上腺素的放射性百分比与上皮中的相似或更高。以每毫克组织计算,在给药后的前130分钟内,上皮中氯霉素加代谢物的浓度显著高于基质-内皮。虽然这些药物的物理性质决定了上皮或基质-内皮中哪种药物浓度更高,但基质-内皮的质量比上皮大九倍,使其成为整个组织水平上的主要药物储存库。瞬膜的存在与否对上皮、基质-内皮或房水中任何一种药物的水平影响很小。

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引用本文的文献

1
Treatment of ocular infections with topical antibacterials.局部应用抗菌药物治疗眼部感染。
Clin Pharmacokinet. 1999 Nov;37(5):351-60. doi: 10.2165/00003088-199937050-00001.
2
ICI 118,551: an effective ocular hypotensive agent with selectivity for the ciliary process beta 2-adrenoceptor and with minimal cardiac side effects.ICI 118,551:一种有效的降眼压药物,对睫状突β2肾上腺素能受体具有选择性,且心脏副作用极小。
Br J Pharmacol. 1984 Nov;83(3):821-9. doi: 10.1111/j.1476-5381.1984.tb16238.x.