THE MDR1 GENE-PRODUCT, P-GLYCOPROTEIN, MEDIATES THE TRANSPORT OF THE CARDIAC GLYCOSIDE, DIGOXIN
THE MDR1 GENE-PRODUCT, P-GLYCOPROTEIN, MEDIATES THE TRANSPORT OF THE CARDIAC GLYCOSIDE, DIGOXIN
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DOI：
10.1016/0006-291x(92)91593-f
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发表时间：
1992-11-30
影响因子：
3.1
通讯作者：
SILVERMAN, M
中科院分区：
文献类型：
--
作者：
DELANNOY, IAM;SILVERMAN, M
地高辛是一种广泛使用的心脏糖苷，治疗指数低，已知与一大群不同的联合给药药物相互作用，经常导致糖苷的毒性积累。因此，建立这些相互作用的机制(S)具有潜在的临床意义。目前的研究表明，在多药耐药细胞中过度表达的mdr1基因产物P-糖蛋白是导致地高辛肾脏分泌的顶膜蛋白，并为某些联合用药时地高辛中毒的发生提供了解释。由于地高辛被认为是内源性洋地黄样糖苷的原型，该结果也允许推测内源性洋地黄样糖苷可能是P-gp的天然底物。
Digoxin, a widely used cardiac glycoside with a low therapeutic index, is known to interact with a large and diverse group of co-administered drugs, frequently leading to toxic accumulation of the glycoside. Establishing the mechanism(s) of these interactions, therefore, has potential clinical significance. The present studies implicate P-glycoprotein, the MDR1 gene product overexpressed in multidrug resistant cells, as the apical membrane protein responsible for the renal secretion of digoxin and provide an explanation for the occurrence of digoxin toxicity in the presence of certain co-administered medications. Since digoxin is considered a prototype for endogenous digitalis-like glycosides, the results also allow for speculation that endogenous digitalis-like glycosides may be the natural substrates for P-gp.