A redox-based chemical delivery system that enhances estradiol distribution to the brain: disposition studies in the rat.
A redox-based chemical delivery system that enhances estradiol distribution to the brain: disposition studies in the rat.
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一种基于氧化还原的化学输送系统，可增强雌二醇向大脑的分布：大鼠的处置研究。
DOI：
10.1023/a:1015814720778
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发表时间：
1991
影响因子：
3.7
通讯作者：
Derendorf,H
中科院分区：
文献类型：
--
作者：
Estes,KS;Keuth,V;Dietzel,K;Brewster,ME;Bodor,NS;Derendorf,H
研究了基于氧化还原二氢吡啶-吡啶盐转化的雌二醇化学给药系统（E2-CDS）在大鼠体内的处置。在静脉内给予配制为改性环糊精包合物的E2-CDS后1 - 14天，评价E2-CDS和氧化代谢产物（E2-Q+）的组织和血浆浓度。虽然给药后1天所有样品的E2-CDS水平均低于HPLC测定检测限，但E2-Q+易于定量。E2-Q+的计算半衰期在脑组织中最长，在心脏、肺和肾组织中显著较短，在血浆中最短。E2-CDS给药剂量与给药后24小时采集的脑和其他组织中测定的氧化代谢物之间存在线性关系。同时给予高剂量的二甲基亚砜（DMSO）溶剂中的类似可氧化的二氢吡啶、1-甲基-1，4-二氢烟酰胺（NMN）可降低脑和其他组织中测定的E2-Q+，但不会显著影响这些组织中的相对分布模式。氧化代谢产物给药后未检测到脑组织E2 Q+水平。
The disposition of a chemical delivery system for estradiol (E2-CDS) which is based on a redox dihydropyridine-pyridinium salt conversion was investigated in rats. Tissue and plasma concentrations of E2-CDS and the oxidized metabolite (E2-Q+) were evaluated at times ranging from 1 to 14 days after intravenous administration of E2-CDS formulated as a modified cyclodextrin inclusion complex. While E2-CDS levels were below HPLC assay detection limits for all samples by 1 day postdosing, E2-Q+was readily quantified. The calculated half-life of E2-Q+was longest in brain tissue, significantly shorter in heart, lung, and kidney tissues, and shortest in plasma. There was a linear relationship between administered E2-CDS dose and oxidized metabolite measured in brain as well as in other tissues collected 24 hr after drug administration. Coadministration of high doses of a similarly oxidizable dihydropyridine, l-methyl-1,4-dihydronicotinamide (NMN), in a dimethylsulfoxide (DMSO) vehicle decreased E2-Q+measured in brain and other tissues without significantly affecting the relative patterns of distribution in these tissues. Brain tissue E2Q+levels were not detected after dosing with the oxidized metabolite.