脑增强雌二醇化学输送系统的组织分布。

Drug design and delivery Pub Date : 1990-05-01
M H Rahimy, J W Simpkins, N Bodor
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引用次数: 0

摘要

增强雌二醇(E2)在大脑中的传递和持续释放可能在有效治疗血管舒缩性潮热和前列腺癌方面具有潜在的临床应用。因此,我们评估了一种脑增强的e2 -化学传递系统(E2-CDS),该系统基于可相互转换的二氢吡啶与吡啶盐氧化还原反应平衡。在这项研究中,我们评估了E2- q +和E2的组织分布——E2- cds的无活性和活性代谢物。所有组织均检测到E2- q +和E2。外周组织中E2- q +和E2被迅速清除,但在脑组织中,这两种化合物的浓度都呈现缓慢下降,时间为t1/2 = 8天。服用E2-CDS 14天后,脑内E2-Q+水平比血浆水平高170倍,脂肪水平高20倍,肝脏水平高8倍。同样,大脑e2水平比血浆水平高出38倍,脂肪水平高出11倍,肝脏水平高出7倍。此外,E2-Q+在垂体前叶、肾脏、心脏和肺中的水平最初比脑中的水平高2- 6倍,但在给予E2-CDS 14天后,脑中的E2-Q+水平比这些外周组织中的E2-Q+水平高出1.5- 3倍。E2- cds处理的大鼠E2- q +和E2的脑/外周组织比例增加,支持脑增强传递和E2从该传递系统持续释放。
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Tissue distribution of a brain-enhanced chemical delivery system for estradiol.

Enhanced delivery and sustained release of estradiol (E2) in the brain could have potential clinical applications in the effective treatment of vasomotor "hot flushes" and prostatic cancer. We have, therefore, evaluated a brain-enhanced E2-chemical delivery system (E2-CDS), which is based upon the interconvertible dihydropyridine in equilibrium with pyridinium salt redox reaction. In this study, we evaluated the tissue distributions of E2-Q+ and E2--the inactive and active metabolites of the E2-CDS. Both E2-Q+ and E2 were detected in all tissues analyzed. In peripheral tissues, E2-Q+ and E2 were rapidly cleared, but in brain, concentrations of both compounds exhibited a slow decline with a t1/2 = 8 days. 14 Days after the E2-CDS administration, brain levels of E2-Q+ exceeded plasma levels by 170-fold, fat levels by 20-fold, and liver levels by 8-fold. Similarly, brain-E2 levels exceeded plasma levels by 38-fold, fat levels by 11-fold, and liver levels by 7-fold. Furthermore, levels of E2-Q+ In anterior pituitary, kidney, heart, and lung were initially 2- to 6-fold higher than brain levels, but 14 days after the E2-CDS administration, brain levels of E2-Q+ exceeded E2-Q+ levels in these peripheral tissues by 1.5- to 3-fold. The increased brain/peripheral tissues ratios of E2-Q+ and E2 in rats treated with the E2-CDS support brain-enhanced delivery and sustained release of E2 from this delivery system.

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