Clinical Consequences of the Lipophilicity and Plasma Protein Binding of Antiarrhythmic Drugs and Active Metabolites in Man
Clinical Consequences of the Lipophilicity and Plasma Protein Binding of Antiarrhythmic Drugs and Active Metabolites in Man
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抗心律失常药物和活性代谢物的亲脂性和血浆蛋白结合对人体的临床影响
DOI：
10.1111/j.1749-6632.1984.tb14507.x
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发表时间：
1984
影响因子：
5.2
通讯作者：
D. Drayer
中科院分区：
文献类型：
--
作者：
D. Drayer
在两个系列抗心律失常的药物测试,随着辛醇/水分配系数的增加所以做以下:消除体内的生物转化,初步的生物转化在口服后肝脏和胃肠道,蛋白结合在某种程度上,并渗透到脑组织。接受亲脂性β -肾上腺受体阻断药物的患者可能比接受亲水β受体阻断药物的患者中枢神经系统副作用更大。在生物同质性概念的指导下，药物的结构修饰可以使治疗活性与毒性活性分离。α -1酸性糖蛋白是结合基本抗心律失常药物的主要血浆蛋白。抗心律失常药物的代谢物通常比母体药物更具极性（亲脂性更低）和更少的血浆蛋白结合。
In two series of antiarrhythmic drugs tested, as the octanol/water partition coefficient increases so do the following: elimination from the body by biotransformation, first-pass biotransformation in the liver and gastrointestinal tract after oral administration, protein binding to some extent, and penetration into brain tissue. Patients receiving lipophilic beta-adrenoreceptor blocking drugs may experience more central nervous system side effects than those receiving hydrophilic beta blockers. Structural modification of a drug, guided by the concept of bioisosterism, may allow the disassociation of therapeutic from toxic activities. Alpha-1 acid glycoprotein is the major plasma protein that binds the basic antiarrhythmic drugs. Antiarrhythmic drug metabolites are generally more polar (less lipophilic) and less plasma protein-bound than the parent drugs.