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肝移植受者与供体肝脏 CYP3A 基因型的差异及他克莫司剂量的调整。

Differences in CYP3A genotypes of a liver transplant recipient and the donor liver graft and adjustment of tacrolimus dose.

机构信息

Department of Hospital Pharmacy, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.

Department of Clinical Chemistry, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

Br J Clin Pharmacol. 2019 Aug;85(8):1852-1854. doi: 10.1111/bcp.13958. Epub 2019 Jun 12.

Abstract

Tacrolimus (Tac) is well established as main immunosuppressant in most immunosuppressive regimens in solid organ transplantation. Due to the narrow therapeutic window, pre dose Tac levels (C0) are monitored in all patients receiving Tac to reach optimal therapeutic levels. Tac is metabolized in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. We present a case of an African American woman who underwent a liver transplantation in which adequate Tac levels were difficult to accomplish due to differences in cytochrome P450 3A4/5 (CYP3A4/5) polymorphisms of the transplant recipient and the donor liver graft. This case report highlights that genotyping the liver transplant recipient and the donor liver graft might provide data which could be used to predict the tacrolimus metabolism post transplantation.

摘要

他克莫司(Tac)在实体器官移植中大多数免疫抑制方案中被广泛用作主要免疫抑制剂。由于治疗窗较窄,因此所有接受他克莫司治疗的患者都需要监测其药物谷浓度(C0)以达到最佳治疗水平。他克莫司在肝脏和肠道中通过细胞色素 P450 3A(CYP3A)同工酶 CYP3A4 和 CYP3A5 代谢。我们报告了 1 例美国非洲裔妇女的病例,由于移植受者和供体肝移植物细胞色素 P450 3A4/5(CYP3A4/5)多态性的差异,导致她难以达到足够的他克莫司水平。本病例报告强调,对肝移植受者和供体肝移植物进行基因分型可能提供可用于预测移植后他克莫司代谢的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fd9/6624396/911355be6d17/BCP-85-1852-g001.jpg

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