Hasegawa Yoshinori
Dept. of Medicine, Division of Respiratory Diseases, Nagoya University Graduate School of Medicine.
Gan To Kagaku Ryoho. 2003 Mar;30(3):325-33.
Dose adjustment of drug administration for each patient has been performed based on counts of some factors such as body surface area, age of the patient, performance status, renal and/or liver function. Pharmacokinetic and pharmacodynamic analyses have been investigated by measuring the plasma concentration of a drug and observing the drug effects. However, prior to drug administration it is difficult to predict unexpected, severe drug toxicity, which depends on the individual differences among patients. Recent progress in human genome analysis has been providing tools for new approaches to disease treatment based on individual differences using genetic information. This review focuses on the drug metabolizing enzyme and its genetic polymorphisms in cancer chemotherapy. We describe the recent findings on pharmacogenomics between toxicity and the genetic polymorphisms of the thiopurine methyltransferase (TPMT) gene, dihydropyrimidine dehydrogenase (DPYD) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and uridine diphosphate glucuronosyltransferase (UGT1A1 and UGT1A7) gene. We need to accumulate clinical data based on the variation of genetic profiling as well as pharmacogenetic information. Such data will help tailor cancer chemotherapy to an individual's predisposition in the near future.
每位患者的药物给药剂量调整是根据一些因素的计数来进行的，如体表面积、患者年龄、身体状况、肾和/或肝功能。通过测量药物的血浆浓度并观察药物效果，对药代动力学和药效学进行了分析。然而，在给药前很难预测意外的严重药物毒性，这取决于患者之间的个体差异。人类基因组分析的最新进展为基于个体差异利用遗传信息进行疾病治疗的新方法提供了工具。本综述重点关注癌症化疗中的药物代谢酶及其基因多态性。我们描述了近期关于硫嘌呤甲基转移酶（TPMT）基因、二氢嘧啶脱氢酶（DPYD）基因、亚甲基四氢叶酸还原酶（MTHFR）基因以及尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1和UGT1A7）基因的药物基因组学在毒性与基因多态性之间的研究发现。我们需要基于基因图谱的变化以及药物遗传学信息积累临床数据。这些数据将有助于在不久的将来根据个体易感性定制癌症化疗方案。
