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[药物遗传学:药代动力学及临床意义]

[Pharmacogenetics: pharmacokinetics and clinical implications].

作者信息

Blardi P

机构信息

Istituto di Clinica Medica Generale e Terapia Medica, Nuovo Policlinico Le Scotte, Siena.

出版信息

Recenti Prog Med. 1997 Jan;88(1):46-55.

PMID:9102716
Abstract

In the last years, pharmacogenetic studies tried to identify the hereditary bases characterizing different individual response to drugs. Human organism tries to remove drugs by activating enzyme systems. Metabolization reaction rate shows wide interindividual variations, being characterized by different factors, such as physiologic (age, sex), pathologic (liver and kidney diseases), and genetic characteristics. Inborn errors may lead to some alterations in functional enzyme activities. These alterations led to divide the whole population into two groups: slow metabolizers PM (having a slow metabolism), and fast metabolizers EM (having a normal metabolism). Such a different behaviour may lead to changes in pharmacokinetic parameters which may also influence pharmacodynamic characteristics of the drug, thus leading to: 1) an excessive therapeutic effect, 2) a decreased therapeutic effect, 3) an increased toxicity of the drug not undergoing its transformation, 4) toxicity of a metabolic byproduct formed by a pathway different from the main one.

摘要

在过去几年中,药物遗传学研究试图确定不同个体对药物反应特征的遗传基础。人体通过激活酶系统来试图清除药物。代谢反应速率显示出个体间的广泛差异,其特征受不同因素影响,如生理因素(年龄、性别)、病理因素(肝脏和肾脏疾病)以及遗传特征。先天性缺陷可能导致功能性酶活性出现一些改变。这些改变导致整个人口被分为两组:慢代谢者(PM,代谢缓慢)和快代谢者(EM,代谢正常)。这种不同的行为可能导致药代动力学参数的变化,这也可能影响药物的药效学特征,从而导致:1)治疗效果过度;2)治疗效果降低;3)未发生转化的药物毒性增加;4)由不同于主要途径的途径形成的代谢副产物的毒性。

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