他克莫司:药代动力学,药效动力学和药物基因组学

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (9): 1042-1049.

他克莫司:药代动力学,药效动力学和药物基因组学

张月丽¹, 明英姿², 周宏灏¹, 张伟¹

¹ 中南大学湘雅医院临床药理研究所, 中南大学临床药理研究所,湖南省遗传药理学重点实验室, 长沙 410078,湖南;
² 中南大学湘雅三医院器官移植科,长沙 410078,湖南

收稿日期:2013-10-16 修回日期:2014-07-23 出版日期:2014-09-26 发布日期:2014-09-26
通讯作者: 张伟,男,博士,教授,博士生导师,研究方向:遗传药理学与药物基因组学、临床药理学、药物代谢动力学。Tel: 0731-84805380 E-mail: yjsd2003@163.com
作者简介:张月丽,女,硕士,研究方向:临床药理学、遗传药理学和药物基因组学。Tel: 0731-84805380 E-mail: zhangyueli0228@163.com
基金资助:
国家自然科学基金资助项目(81273595); 国家高技术研究发展计划(863 计划)资助项目(2012AA02A518)

Tacrolimus pathways:pharmacokinetics,pharmacodynamics and pharmacogenomics

ZHANG Yue-li¹, MING Ying-zi², ZHOU Hong-hao¹, ZHANG Wei¹

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Central South University,Changsha 410078,Hunan,China;
² Institute of the third Xiangya Hospital, Central South University, Organ transplant center, Changsha 410078,Hunan,China

Received:2013-10-16 Revised:2014-07-23 Online:2014-09-26 Published:2014-09-26

摘要/Abstract

摘要： 他克莫司( FK506) 是一种广泛应用的免疫抑制剂,主要用于器官移植后预防排斥反应。药物基因组学研究基因多态性对药物在体内吸收、代谢、分布和排泄的影响,有助于实现免疫抑制剂的个体化治疗。理解遗传因素对FK506药代动力学和药效动力学的影响能够帮助临床医生制定针对个体的最佳免疫抑制方案,预测早期的最佳起始剂量与维持剂量和识别药物的毒副作用。

关键词: 他克莫司, 药代动力学, 药效动力学, 单核苷酸多态性, 药物基因组学

Abstract: The calcineurin inhibitors tacrolimus is immunosuppressant drug used for the prevention of organ rejection following transplantation. Pharmacogenomics research studying the effects of genetic polymorphisms on drug absorption, metabolism, disposition and response may eventually provide information that can be used in the clinical setting for individualizing immunosuppressant therapy. Understanding the influence of genetic factors on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors could allow identification of the optimal immunosuppressant drug combination for a particular individual, assist in early prediction of the optimal starting dose and maintenance regimen, and help identify patients with an increased risk of drug inefficacy or side effects.

Key words: tacrolimus, pharmacokinetics, pharmacodynamics, single nucleotide polymorphisms, pharmacogenomics

中图分类号:

R969

张月丽, 明英姿, 周宏灏, 张伟. 他克莫司:药代动力学,药效动力学和药物基因组学[J]. 中国临床药理学与治疗学, 2014, 19(9): 1042-1049.

ZHANG Yue-li, MING Ying-zi, ZHOU Hong-hao, ZHANG Wei. Tacrolimus pathways:pharmacokinetics,pharmacodynamics and pharmacogenomics[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(9): 1042-1049.

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