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白蛋白和α-1酸性糖蛋白对离体灌注大鼠肝脏中哌唑嗪和安替比林消除的影响。

Effects of albumin and alpha-1 acid glycoprotein on elimination of prazosin and antipyrine in the isolated perfused rat liver.

作者信息

Oie S, Fiori F

出版信息

J Pharmacol Exp Ther. 1985 Sep;234(3):636-40.

PMID:4032284
Abstract

This study was undertaken to investigate the effect of albumin and alpha-1 acid glycoprotein on the elimination of drugs with a low extraction ratio in the isolated perfused rat liver. The unbound clearance of prazosin increased 69% after the addition of 14 mg/ml of albumin to the perfusate whereas the unbound clearance decreased by 51% after the addition of 0.85 mg/ml of alpha-1 acid glycoprotein. The clearance of antipyrine, a compound not bound to albumin or alpha-1 acid glycoprotein, increased 28% in the presence of albumin but was not altered in the presence of alpha-1 acid glycoprotein. These results suggest that albumin has the ability to enhance the elimination of drugs both bound and not bound to albumin. This effect was found not to be related to pH changes across the liver or to the oncotic pressure effect of albumin. Alpha-1 acid glycoprotein, on the other hand, seems to be able to decrease the elimination of drugs which bind to it, but has no effect on drugs that are not bound.

摘要

本研究旨在探讨白蛋白和α-1酸性糖蛋白对离体灌注大鼠肝脏中低摄取率药物消除的影响。向灌注液中添加14mg/ml白蛋白后,哌唑嗪的非结合清除率增加了69%,而添加0.85mg/mlα-1酸性糖蛋白后,非结合清除率降低了51%。安替比林是一种不与白蛋白或α-1酸性糖蛋白结合的化合物,在有白蛋白存在时其清除率增加了28%,但在有α-1酸性糖蛋白存在时未发生改变。这些结果表明,白蛋白具有增强与白蛋白结合及未结合药物消除的能力。发现这种作用与肝脏跨膜pH变化或白蛋白的胶体渗透压效应无关。另一方面,α-1酸性糖蛋白似乎能够降低与其结合药物的消除,但对未结合药物没有影响。

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