Introduction to Drug Metabolism
Introduction to Drug Metabolism
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DOI：
10.1002/9783527630905.ch10
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
U. Zanger
中科院分区：
文献类型：
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作者：
U. Zanger
临床使用的大多数药物，以及许多用于娱乐目的的药物和其他外来物质，都具有亲脂性，因为否则它们不会被充分吸收。一旦进入系统，亲脂性物质很难被肾脏消除，并且它们在较长时间内的持续吸收将导致它们在身体的细胞膜和脂肪沉积物中积累。事实上，在不转化为更亲水的产品的情况下，非常亲脂的化学品的消除半衰期可以是几年的数量级。因此，药物代谢（也称为异生物质生物转化）的主要功能是增加进入体内的异物的亲水性，以便使其能够通过肾脏或肠道有效消除（图10.1）。通常，但并不总是，这一过程与药理活性的丧失同时进行;因此，解毒一词被用作另一个同义词。然而，药物代谢也可能导致有毒代谢物，称为生物降解。在药物治疗中，重要的是通过在所谓的治疗窗内达到稳态血浆浓度来平衡积极和消极的影响，在治疗窗内药物已被证明具有药理学作用而不会“过量”或“剂量不足”的浓度范围。
Most drugs in clinical use, but also many drugs used for recreational purposes and other foreign substances, have lipophilic properties, because otherwise they would not be sufficiently absorbed. Once in the system, lipophilic substances are difficult to eliminate by the kidneys, and their continuous uptake over longer periods would lead to their accumulation in cell membranes and fat deposits of the body. In fact, without conversion into more hydrophilic products, the elimination half-life of very lipophilic chemicals can be of the order of several years. It is thus the major function of drug metabolism, also referred to as xenobiotic biotransformation, to increase the hydrophilicity of foreign substances that have entered the body, in order to enable their efficient elimination through the kidneys or the intestine (Figure 10.1). Often, but not always, this process goes in parallel with a loss of pharmacological activity; hence, the term detoxification is in use as another synonym. However, drug metabolism can also lead to toxic metabolites, referred to as biotoxification. In drug therapy, it is important to balance out positive and negative effects by reaching a steady-state plasma concentration within the socalled therapeutic window–a concentration range where the drug has proven pharmacological effect without being “overdosed” or “underdosed.”