Gerloff T, Roots I
Institut für Klinische Pharmakologie, Charité Universitätsmedizin Berlin.
Internist (Berl). 2005 Nov;46(11):1270-7. doi: 10.1007/s00108-005-1489-3.
Pharmacogenetics as one of the areas of clinical pharmacology addresses hereditary factors involved in individually different responses to drugs. Clinical trials combined with molecular genetics seek for underlying reasons influencing efficacy and toxicity of drugs. The declared goal of pharmacogenetics is to provide physicians with knowledge and tools to allow an individualized patient-directed pharmacotherapy. This concept is best evolved for clinical practice in the field of drug-metabolizing enzymes, especially for the cytochromes P450 (CYP) 2D6, CYP2C19 and thiopurine S-methyltransferase (TPMT). Patients with inherited enzyme deficiencies are at risk to accumulate excessive drug concentrations when treated with standard doses which may lead to adverse drug reactions or even to life-threatening conditions. Genetic factors are also involved in drug-target interactions (e. g. receptors). Prospective controlled clinical trials are needed to evaluate the benefit of pharmacogenetics for therapy outcome and to define its role in clinical practice.
药物遗传学作为临床药理学的一个领域,研究个体对药物产生不同反应所涉及的遗传因素。临床试验与分子遗传学相结合,探寻影响药物疗效和毒性的潜在原因。药物遗传学宣称的目标是为医生提供知识和工具,以实现针对患者个体的药物治疗。这一概念在药物代谢酶领域,尤其是细胞色素P450(CYP)2D6、CYP2C19和硫嘌呤S-甲基转移酶(TPMT)方面,最适合临床实践。遗传性酶缺乏的患者在接受标准剂量治疗时,有药物浓度过度蓄积的风险,这可能导致药物不良反应甚至危及生命的情况。遗传因素也参与药物-靶点相互作用(如受体)。需要进行前瞻性对照临床试验,以评估药物遗传学对治疗结果的益处,并确定其在临床实践中的作用。