Yamamoto I, Azuma J
Department of Clinical Evaluation of Medicines and Therapeutics, Faculty of Pharmaceutical Sciences, Osaka University.
Nihon Rinsho. 1998 Mar;56(3):579-83.
This brief review discusses the relationship between genetic polymorphism of drug metabolizing enzyme and drug's safety and efficacy. When elimination occurs via a single metabolic pathway, individual differences in metabolic rates can lead to large differences in drug and metabolite concentrations in the blood. Genetic polymorphism leads to subpopulation of patients with decreased, absent or even increased activities of certain reactions (e.g., CYP2C19, CYP2D6, CYP2C9, N-acetyltransferase, thiopurine methyltransferase polymorphism). The consequences of a genetic polymorphism include not only altered kinetics of specific drug substrate but idiosyncratic adverse drug reactions. Having these information will aid in determining dosage of certain medications to the patients with an inherited abnormality of drug metabolizing enzyme. Pharmacogenetics already has influenced therapeutics.
本简要综述讨论了药物代谢酶的基因多态性与药物安全性和有效性之间的关系。当通过单一代谢途径进行消除时，代谢速率的个体差异可导致血液中药物和代谢物浓度的巨大差异。基因多态性导致特定反应活性降低、缺失甚至增加的患者亚群（例如，CYP2C19、CYP2D6、CYP2C9、N - 乙酰转移酶、硫嘌呤甲基转移酶多态性）。基因多态性的后果不仅包括特定药物底物动力学的改变，还包括特异质性药物不良反应。掌握这些信息将有助于确定对患有遗传性药物代谢酶异常的患者使用某些药物的剂量。药物遗传学已经对治疗产生了影响。
