DRUG TRANSFER ACROSS THE BLOOD-BRAIN-BARRIER - CORRELATION BETWEEN INVITRO AND INVIVO MODELS
DRUG TRANSFER ACROSS THE BLOOD-BRAIN-BARRIER - CORRELATION BETWEEN INVITRO AND INVIVO MODELS
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DOI：
10.1111/j.1471-4159.1992.tb10055.x
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发表时间：
1992-05-01
影响因子：
4.7
通讯作者：
TILLEMENT, JP
中科院分区：
文献类型：
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作者：
DEHOUCK, MP;JOLLIETRIANT, P;TILLEMENT, JP
为了评估药物通过血脑屏障（BBB）的转运，我们比较了使用体外或体内方法获得的0时最大脑提取值[E（0）值]。体外血脑屏障模型由在滤器一侧生长的脑毛细血管内皮细胞和在另一侧生长的星形胶质细胞的共培养物组成。体内模型采用麻醉大鼠颈动脉内注射。测试了11种化合物。选择它们是因为它们表现出定量上不同的脑提取率：菊粉和蔗糖非常低，昔康相关非甾体类药物和双氯芬酸低，普萘洛尔和地西泮高。由于这些化合物显然是通过被动扩散机制转移的，因此添加了另外两种化合物，葡萄糖和亮氨酸，它们通过已知的载体介导的过程穿过BBB。体内和体外E（0）值显示出强相关性，如斯皮尔曼相关系数（r = 0.88，p < 0.01）所示。这种共培养物可以相对容易地大量生产，这有助于筛选新的中枢作用药物。
To assess the drug transport across the blood-brain barrier (BBB), we compared the maximal brain extraction values at time 0 [E(0) values] obtained using either in vitro or in vivo methods. The in vitro BBB model consisted of a coculture of brain capillary endothelial cells growing on one side of a filter and astrocytes on the other. The in vivo model used intracarotid injection in anesthetized rats. Eleven compounds were tested. They were selected because they exhibit quantitatively different brain extraction rates: very low for inulin and sucrose, low for oxicam-related nonsteroidal antiinflammatory drugs and diclofenac, and high for propranolol and diazepam. As these compounds are apparently transferred by a passive diffusion mechanism, two others, glucose and leucine, were added that cross the BBB by a known carrier-mediated process. The in vivo and in vitro E(0) values showed a strong correlation as indicated by the Spearman's correlation coefficient (r = 0.88, p < 0.01). The relative ease with which such cocultures can be produced in large quantities could facilitate the screening of new centrally acting drugs.