Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP4502C19
Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP4502C19
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DOI：
10.1176/appi.psy.47.1.75
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发表时间：
2006-02-01
期刊：
影响因子：
3.4
通讯作者：
Cozza, KL
中科院分区：
文献类型：
--
作者：
De Leon, J;Armstrong, SC;Cozza, KL
药物遗传学已经进入临床精神病学实践，FDA批准了AmpliChip CYP 450测试，该测试对两个细胞色素P450 2D6（CYP 2D6）和2C19（CYP 2C19）基因进行基因分型。其他药物遗传学测试，包括那些专注于药效基因的测试，还远未准备好用于临床应用。CYP2D6对许多抗抑郁药和抗精神病药的代谢很重要，CY2C19对一些抗抑郁药的代谢很重要。缺乏这种酶的弱代谢者（PM）占CYP2D6高加索人的7%，占CYP2C19东亚人的25%。具有三个或三个以上活性CYP2D6等位基因的患者（在北非和中东高达29%）被称为CYP2D6超快代谢者（UM）。CYP2D6表型（特别是PM）可能在服用三环类抗抑郁药（TCA）、文拉法辛、典型抗精神病药和利培酮的患者中很重要。CYP2C19 PM表型在服用TCA类药物以及西酞普兰、依他普仑和舍曲林的患者中可能很重要。根据文献和作者的临床经验，作者提供了识别和治疗CYP2D6 PM、CYP2C19 PM和CYP2D6 UM的临时建议。未来几年将确定CYP2D6基因分型是否对服用新药阿立哌唑、度洛西汀和托莫西汀的患者有益。提供了与提供CYP2D6和CYP2C29基因分型的实验室打交道的实用建议。
Pharmacogenetics has arrived in clinical psychiatric practice with the FDA approval of the AmpliChip CYP450 Test that genotypes for two cytochrome P450 2D6 (CYP2D6) and 2C19 (CYP2C19) genes. Other pharmacogenetic tests, including those focused on pharmacodynamic genes, are far from ready for clinical application. CYP2D6 is important for the metabolism of many antidepressants and antipsychotics, and CY2C19 is important for some antidepressant metabolism. Poor metabolizers (PMs), lacking the enzyme, account for up to 7% of Caucasians for CYP2D6 and up to 25% of East Asians for CYP2C19. Patients having three or more active CYP2D6 alleles (up to 29% in North Africa and the Middle East), are called CYP2D6 ultrarapid metabolizers (UMs). CYP2D6 phenotypes (particularly PMs) are probably important in patients taking tricyclic antidepressants (TCAs), venlafaxine, typical antipsychotics, and risperidone. The CYP2C19 PM phenotype is probably important in patients taking TCAs and perhaps citalopram, escitalopram, and sertraline. On the basis of the literature and the authors' clinical experience, the authors provide provisional recommendations for identifying and treating CYP2D6 PMs, CYP2C19 PMs, and CYP2D6 UMs. The next few years will determine whether CYP2D6 genotyping is beneficial for patients taking the new drugs aripiprazole, duloxetine, and atomoxetine. Practical recommendations for dealing with laboratories offering CYP2D6 and CYP2C29 genotyping are provided.