遗传药理学的作用在抗癫痫药物的代谢:药代动力学和治疗意义。

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克洛茨U

遗传药理学的作用在抗癫痫药物的代谢:药代动力学和治疗意义。

Pharmacokinet。2007; 46 (4): 271 - 9。

PubMed ID

17375979 (在PubMed

]

文摘

几个不同的因素,包括药物基因学,有助于个人间变异性药物反应。像大多数其他代理一样,许多抗癫痫药物(aed)代谢由多种酶反应,和细胞色素P450 (CYP)总科已经吸引了相当大的关注。一些cyp的形式存在于基因(等位基因)变异,也可能影响等离子体浓度或药物暴露(血浆浓度时间曲线下面积(AUC)) aed。关于aed的新陈代谢,多态CYP2C9和CYP2C19感兴趣的。本文总结了证据是否这种多态性影响aed的临床作用。在美芬妥因、缺陷在其代谢可能归因于> 10突变等位基因(指定为* 2 * 3和其他人)的基因表达CYP2C19。因此,穷人metabolisers (PMs)和广泛metabolisers (EMs)可能是有区别的,其频率不同种族人群。CYP2C19有助于安定和苯妥英的新陈代谢,后者代表CYP2C9底物,药物也与主导变量被定义为* 2 * 3。对于AED,最大限度肝消除速率的2倍的区别(如清除)或极端之间的AUC EMs和经前综合症,对于苯妥英(AED狭窄治疗窗口),建议减少剂量只对患者突变等位基因携带者CYP2C19和CYP2C9,这个群体的数量在白种人中非常罕见(约占人口的1%),但更频繁的在亚洲人(大约10%)。的小贡献的新陈代谢CYP2C19苯巴比妥(苯巴比妥)可以被忽略。 In rare cases, valproic acid can be metabolised to the reactive (hepatotoxic) metabolite, 4-ene-valproic acid. It is not yet clear whether genetic variants of the involved enzyme (CYP2C9) are responsible for this problem. Likewise, the active metabolite of carbamazepine, carbamazepine-10,11-epoxide, is transformed by the microsomal epoxide hydrolase, an enzyme that is also highly polymorphic, but the pharmacokinetic and clinical consequences still need to be evaluated. Pharmacogenetic investigations have increased our general knowledge of drug disposition and action. As for old and especially new AEDs the pharmacogenetic influence on their metabolism is not very striking, it is not surprising that there are no treatment guidelines taking pharmacogenetic data into account. Therefore, the traditional and validated therapeutic drug monitoring approach, representing a direct 'phenotype' assessment, still remains the method of choice when an individualised dosing regimen is anticipated. Nevertheless, pharmacogenetics and pharmacogenomics can offer some novel contributions when attempts are made to maximise drug efficacy and enhance drug safety.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Fosphenytoin	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节
Fosphenytoin	细胞色素P450 2 c9	蛋白质	人类	未知的	底物 诱导物	细节