Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants
Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants
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DOI：
10.1038/clpt.2013.2
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发表时间：
2013-05-01
影响因子：
6.7
通讯作者：
Stingl, J. C.
中科院分区：
文献类型：
--
作者：
Hicks, J. K.;Swen, J. J.;Stingl, J. C.
CYP2D6和CYP2C19的多态性影响三环类药物的疗效和安全性，有些药物仅受CYP2D6的影响，而其他药物则受两种多态性酶的影响。阿米替林、氯丙咪嗪、多塞平、丙咪嗪和曲米帕明可被CYP2C19脱甲基化为具有抗肿瘤活性的代谢产物。这些药物及其代谢产物，沿着地昔帕明和去甲替林，通过CYP 2D6羟基化为活性较低的代谢产物。提供了来自已发表文献的三环类抗抑郁药CYP2D6和CYP2C19基因型定向给药的证据。
Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.