Couture Lucie, Nash John A, Turgeon Jacques
Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, Canada, H3C 3J7.
Pharmacol Rev. 2006 Jun;58(2):244-58. doi: 10.1124/pr.58.2.7.
The passage of drugs across cell membranes dictates their absorption, distribution, metabolism, and excretion. This process is determined by several factors including the molecular weight of the compounds, their shape, degree of ionization, and binding to proteins. Accumulation of xenobiotics into tissues does not depend only on their ability to enter cells, but also on their ability to leave them. For instance, the role of efflux transporters such as ATP-binding cassette (ABC) proteins in the disposition of drugs is now well recognized. Actually, ABC transporters act in synergy with drug-metabolizing enzymes to protect the organism from toxic compounds. The most studied transporter from the ABC transporter superfamily, P-glycoprotein, was found to be overexpressed in tumor cells and associated with an acquired resistance to several anticancer drugs. P-glycoprotein, thought at first to be confined to tumor cells, was subsequently recognized to be expressed in normal tissues such as the liver, kidney, intestine, and heart. Even though information remains rather limited on the functional role of ABC transporters in the myocardium, it is hypothesized that they may modulate efficacy and toxicity of cardioactive agents. This review addresses recent progress on knowledge about the ABC transporters in drug disposition and more precisely their role in drug distribution to the heart.
药物跨细胞膜的转运决定了它们的吸收、分布、代谢和排泄。这个过程由几个因素决定，包括化合物的分子量、形状、离子化程度以及与蛋白质的结合。外源性物质在组织中的蓄积不仅取决于它们进入细胞的能力，还取决于它们离开细胞的能力。例如，诸如ATP结合盒（ABC）蛋白等外排转运体在药物处置中的作用现在已得到充分认识。实际上，ABC转运体与药物代谢酶协同作用，以保护机体免受有毒化合物的侵害。ABC转运体超家族中研究最多的转运体P-糖蛋白，被发现在肿瘤细胞中过度表达，并与对几种抗癌药物的获得性耐药有关。P-糖蛋白最初被认为局限于肿瘤细胞，随后被认识到在肝脏、肾脏、肠道和心脏等正常组织中也有表达。尽管关于ABC转运体在心肌中的功能作用的信息仍然相当有限，但据推测它们可能调节心脏活性药物的疗效和毒性。这篇综述阐述了关于ABC转运体在药物处置方面的知识的最新进展，更确切地说是它们在药物向心脏分布中的作用。
