Pharmacogenomics of Immunosuppressants
Pharmacogenomics of Immunosuppressants
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DOI：
10.1007/978-981-15-3895-7_5
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Xiaoyan Qiu;Zhuo Wu;Qinxia Xu;Chang-cheng Sheng;Z. Jiao
中科院分区：
文献类型：
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作者：
Xiaoyan Qiu;Zhuo Wu;Qinxia Xu;Chang-cheng Sheng;Z. Jiao
实体器官移植后患者的长期生存主要取决于免疫抑制剂的合理使用，包括钙调神经磷酸酶抑制剂（例如，环孢菌素A和他克莫司）和抗代谢药物（例如，霉酚酸）。这些药物具有治疗指数窄、药代动力学和药效学个体间和个体差异大等特点，促进了治疗药物监测和个体化治疗的迫切性。药代动力学变异性可部分由转运蛋白和代谢酶基因的遗传多态性解释，例如钙调磷酸酶抑制剂的细胞色素P450（CYP）3A 4/5多态性和麦考酚酸的UDP葡萄糖醛酸转移酶（UGT）1A 9遗传多态性。近年来，遗传多态性在免疫抑制剂药效学中的作用日益受到重视。这些药物遗传学生物标志物的监测为我们提供了一个强有力的方法来制定免疫抑制剂的个体化给药方案。
Long-term survival of patients after solid organ transplantation mainly depends on the rational use of immunosuppressants, including the calcineurin inhibitors (e.g., cyclosporine A and tacrolimus) and antimetabolic drugs (e.g., mycophenolic acid). These drugs are characterized by narrow therapeutic index, large interindividual and individual variabilities in pharmacokinetics and pharmacodynamics, promoting an urgent for therapeutic drug monitoring and individualized therapy. The pharmacokinetic variabilities can be partly explained by the genetic polymorphisms of the transporter and metabolic enzyme genes, such as cytochrome P450 (CYP) 3A4/5 polymorphisms for calcineurin inhibitors and UDP glucuronosyltransferase (UGT) 1A9 genetic polymorphisms for mycophenolic acid. In recent years, genetic polymorphisms in pharmacodynamics of immunosuppressants have been paid increasing attention. Monitoring of these pharmacogenetic biomarkers provides us a powerful approach to develop individualized dosage regimen for the immunosuppressants.