环磷酰胺的药物基因组学研究进展.PDF

药学学报 Acta Pharmaceutica Sinica 20 14, 49 (7): 971 976 ·971 · 磷酰胺的药物基因组学研究进展 * 陈玲燕, 王雪丁, 黄 民 ( 中山大学药学院, 临床药理研究所, 广东 广州 510080) 摘要: 环磷酰胺 (cyclophosphamide, CPA) 作为最常用的烷化剂类抗肿瘤药物, 也常用于自身免疫性疾病及 器官移植后的治疗。CPA 主要通过肝脏的细胞色素P450 酶代谢为活性产物, 从而发挥 理作用。该药具有严重 的毒副作用, 且疗效和不良反应具有显著的个体差异。本文总结 CPA 体内过程相关的代谢酶及转运体等的基 因多态性与CPA 疗效/毒性的相关性, 为进一步的药物基因组学研究提供参考。 关键词: 环磷酰胺; 基因多态性; 细胞色素P450 酶; 转运体 中图分类号: R966 文献标识码: A 文章编号: 0513-4870 (20 14) 07-0971-06 Advances in the research of pharmacogenomics of cyclophosphamide * CHEN Ling-yan, WANG Xue-ding, HUANG Min (Ins titute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China ) Abstract : Cyclophosphamide (CPA) is the most common alkylating antineoplastic agent, as well as a strong immunosuppressant that is frequently applied to autoimmune diseases and organ transplantation. It is metabolized by cytochrome P450 oxidases (CYPs) to its active metabolite which played a critical role in therapy. CPA has serious and even fatal side effects, and its efficacy and adverse reactions are significantly varied among individuals. In this review, the association of the genetic polymorphisms in the metabolic enzymes and transporters involved in the disposition of CPA with the efficacy and adverse effects of CPA were summarized, thereby providing fundamental reference for further pharmacogenomic study of CPA.