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基于药物遗传学的新治疗理念。

Pharmacogenetics-based new therapeutic concepts.

作者信息

Roots Ivar, Gerloff Thomas, Meisel Christian, Kirchheiner Julia, Goldammer Mark, Kaiser Rolf, Laschinski Gabriele, Brockmöller Jürgen, Cascorbi Ingolf, Kleeberg Ullrich, Hildebrandt Alfred G

机构信息

Institut für Klinische Pharmakologie, Charité-Universitätsmedizin Berlin, Campus Charitè Mitte, Humboldt-Universität zu Berlin, Berlin, Germany.

出版信息

Drug Metab Rev. 2004 Oct;36(3-4):617-38. doi: 10.1081/dmr-200033458.

Abstract

Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.

摘要

药物遗传学是临床药理学的一个领域,研究遗传因素如何影响药物反应。如果在开始药物治疗前适当考虑遗传特征,就可以根据个体患者的需求来调整药物类型及其剂量。药物遗传学为医生的治疗方法增添了相当程度的严格性。如今,药物代谢酶(如细胞色素P450(CYP)2D6和CYP2C19)或药物转运体(如P-糖蛋白)的剂量需求与基因变异之间的关系得到了最充分的证实。如果酶活性缺乏或微弱,标准剂量会比平时带来更多不良反应。然而,有时由于药物浓度较高,治疗反应可能会更好:用于根除幽门螺杆菌的质子泵抑制剂在携带缺陷型CYP2C19变体的患者中更有效。药物与其靶点(如受体)的相互作用也取决于遗传因素。在某些情况下,基因检测有助于区分特定药物治疗的反应者和无反应者。首批药物遗传学检测已经上市。

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