A redox-based system that enhances delivery of estradiol to the brain: pharmacokinetic evaluation in the dog.
A redox-based system that enhances delivery of estradiol to the brain: pharmacokinetic evaluation in the dog.
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一种基于氧化还原的系统，可增强雌二醇向大脑的输送：狗的药代动力学评估。
DOI：
10.1023/a:1015977319212
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发表时间：
1990
影响因子：
3.7
通讯作者：
Derendorf,H
中科院分区：
文献类型：
--
作者：
Dietzel,K;Keuth,V;Estes,KS;Brewster,ME;Clemmons,RM;Vistelle,R;Bodor,NS;Derendorf,H
研究了二氢吡啶-吡啶盐型脑靶向给药系统(CDS)在犬体内的药代动力学。在体外评估的参数包括缓冲液和生物液中的稳定性以及血浆蛋白结合。在活体研究中，检测了血浆、尿液、脑脊液以及选定脑区的药物和代谢物浓度。给药的亲脂性E2-CDS很快就从血浆中消失，在尿液中也检测不到。氧化形式的药物，E2-Q+，在长达2周的时间里没有变化地或以结合物的形式在尿中排泄。后来，血浆水平低于化验检测限值。尿液中E2-Q+浓度的药代动力学分析使半衰期估计为2.2天。尿中的E2-Q+排泄量与剂量成正比，但平均只占剂量的13.9%，这表明必须考虑其他排泄途径。脑脊液中E_2-CDS和E_2-Q~+的浓度均低于检测限值，然而，在给药后1天或3天，个别动物的几个脑区中E_2-Q~+的浓度是相似的。
The pharmacokinetics of a dihydropyridine–pyridinium salt-type chemical delivery system (CDS) for brain-targeted delivery of estradiol (E2) were examined in dogs. Parameters evaluatedin vitroincluded stability in buffers and biological fluids and plasma protein binding.In vivostudies examined drug and metabolite concentrations in plasma, urine, and cerebrospinal fluid as well as in selected brain regions. The administered lipophilic E2-CDS disappeared very quickly from plasma and was not detected in urine. The oxidized drug form, E2-Q+, was excreted unchanged or as a conjugate in the urine for as long as 2 weeks. Plasma levels were below assay detection limits at later times. Pharmacokinetic analysis of urine E2-Q+levels allowed estimation of a half-life of 2.2 days. Amounts of E2-Q+excreted into the urine were proportional to the dose but averaged only 13.9% of the dose, indicating that other routes of excretion must be considered. CSF levels were below the limit of detection for both E2-CDS and E2-Q+, however, brain tissue concentrations of E2-Q+were similar in several brain regions of individual animals examined 1 or 3 days after drug dosing.