Significance of ethnic factors in immunosuppressive therapy management after organ transplantation.
Significance of ethnic factors in immunosuppressive therapy management after organ transplantation.
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DOI：
10.1097/ftd.0000000000000748
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发表时间：
2020-02
影响因子：
2.5
通讯作者：
Takaaki Yamada;Mengyu Zhang;S. Masuda
中科院分区：
文献类型：
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作者：
Takaaki Yamada;Mengyu Zhang;S. Masuda
在过去的二十年里，随着免疫抑制药物如钙调磷酸酶抑制剂、抗增殖剂和雷帕霉素哺乳动物靶点抑制剂的发现和开发，器官移植后的临床结果有了很大的改善。然而，这些药物的个体化给药方案尚未完全建立，除了基于治疗药物监测的剂量调整，由于免疫抑制药物药代动力学的广泛个体间差异。免疫抑制药物药代动力学的变化归因于肝脏和小肠中细胞色素P450酶、UDP-葡萄糖醛酸转移酶和ATP结合盒亚家族B成员1（称为P-糖蛋白或多药耐药1）功能活性的个体间差异。已发现一些遗传变异至少在某种程度上涉及移植后免疫抑制治疗的药代动力学变化。众所周知，次要等位基因的频率和效应大小在不同的种族之间差异很大。因此，种族因素可能为器官移植后优化个体化免疫抑制治疗提供有用的信息。在这里，我们回顾种族因素影响的药代动力学的免疫抑制药物，需要治疗药物监测，包括他克莫司，环孢素，霉酚酸酯，西罗莫司，依维莫司。
Clinical outcomes after organ transplantation have greatly improved in the last two decades with the discovery and development of immunosuppressive drugs such as calcineurin inhibitors, antiproliferative agents, and mammalian target of rapamycin inhibitors. However, individualized dosage regimens have not yet been fully established for these drugs except for therapeutic drug monitoring-based dosage modification due to extensive interindividual variations in immunosuppressive drug pharmacokinetics. The variations in immunosuppressive drug pharmacokinetics are attributed to interindividual variations in the functional activity of cytochrome P450 enzymes, UDP-glucuronosyltransferases, and ATP-binding cassette subfamily B member 1 (known as P-glycoprotein or multidrug resistance 1) in the liver and small intestine. Some genetic variations have been found to be involved to at least some degree in pharmacokinetic variations in post-transplant immunosuppressive therapy. It is well known that the frequencies and effect size of minor alleles vary greatly between different races. Thus, ethnic considerations might provide useful information for optimizing individualized immunosuppressive therapy after organ transplantation. Here, we review ethnic factors affecting the pharmacokinetics of immunosuppressive drugs requiring therapeutic drug monitoring, including tacrolimus, cyclosporine, mycophenolate mofetil, sirolimus, and everolimus.