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与许多传统药物的高水溶性不同,新候选药物常为高脂溶性化合物。血液的水性环境是疏水性药物处置的不良热力学环境。然而,药物与循环中脂蛋白结合可以克服此种困难。阐明这些机制,即药物与脂蛋白结合及脂蛋白包裹的药物在血液和组织中的分配,有利于洞察控制这些化合物药理活性和潜在毒性的因素。本文讨论疏水性药物和脂蛋白相互作用对各种疏水性化合物药代动力学性质、代谢、组织分布及生物活性的影响,扼要指出如何使用这些信息来发现和开发药物。
Unlike many traditional medicines that are highly water-soluble, new drug candidates are often fat-soluble compounds. The aqueous environment of the blood is a poor thermodynamic environment for hydrophobic drug disposal. However, the combination of drugs with circulating lipoproteins can overcome this difficulty. The elucidation of these mechanisms, that is, the drug-lipoprotein-binding and lipoprotein-coated drugs in the blood and tissues, facilitates insight into the factors that control the pharmacological and potentially toxic effects of these compounds. This article discusses the effects of hydrophobic drug-lipoprotein interactions on the pharmacokinetic properties, metabolism, tissue distribution, and bioactivity of various hydrophobic compounds and outlines how to use this information to discover and develop drugs.