Brain mitochondrial drug delivery: influence of drug physicochemical properties.
Brain mitochondrial drug delivery: influence of drug physicochemical properties.
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DOI：
10.1007/s11095-011-0532-4
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发表时间：
2011-11
影响因子：
3.7
通讯作者：
Kompella UB
中科院分区：
文献类型：
--
作者：
Durazo SA;Kadam RS;Drechsel D;Patel M;Kompella UB
为了确定药物理化性质对20种药物在生理ph下脑线粒体递送的影响。分别测定8种阳离子药物（β受体阻阻剂）、6种中性药物（皮质类固醇）和6种阴离子药物（非甾体抗炎药、非甾体抗炎药）对离体大鼠脑线粒体的递送情况。使用多元线性回归来确定亲脂性（Log D）、电荷、极化率、极性表面积（PSA）和分子量是否影响线粒体递送。受体阻滞剂、皮质类固醇和非甾体抗炎药的Log D分别在- 1.41 ~ 1.37、0.72 ~ 2.97和- 0.98 ~ 2之间。每一类药物的线粒体摄取百分比随Log D的增加呈指数增长，在给定的亲脂性下，摄取服从阳离子b>阴离子>中性的顺序。缬霉素降低了膜电位和带正电荷的心得安和倍他洛尔的传递。组合数据集的最佳方程为Log % Uptake=0.333 Log D+ 0.157 Charge - 0.887 Log PSA+2.032 （R2=0.738）。药物亲脂性、电荷、极性表面积和膜电位影响线粒体药物递送，带正电的亲脂分子的吸收效率最高。
To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH. The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery. The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of −1.41 to 1.37, 0.72 to 2.97, and −0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationic>anionic>neutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake=0.333 Log D+ 0.157 Charge – 0.887 Log PSA+2.032 (R2=0.738). Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient.
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影响因子：
15.3
作者：
Sionov, Ronit Vogt;Cohen, Orly;Kfir, Shlomit;Zilberman, Yael;Yefenof, Eitan
通讯作者：
Yefenof, Eitan
影响因子：
3.5
作者：
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Rustin, P
影响因子：
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作者：
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DOI：
10.1073/pnas.0903250106
发表时间：
2009-06-30
影响因子：
11.1
作者：
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通讯作者：
Murphy, Michael P.
DOI：
10.1016/j.jchromb.2008.12.027
发表时间：
2009-01-15
影响因子：
3
作者：
Kadam, Rajendra S.;Kompella, Uday B.
通讯作者：
Kompella, Uday B.