2017-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651757摘要：背景Tacrolimus（TAC）是器官移植最重要的免疫抑制劑，有些病人之劑量與血中濃度難以預測與調整，臨床上相當困擾。TAC 的藥動學受許多臨床因素影響。國外文獻顯示ABCB1、CYP3A4、CYP3A5、POR 基因多型性可能影響TAC 的藥動學，且在亞洲人有足夠比例的變異。在肝臟移植者，因為TAC 主要經由肝臟代謝，因此捐贈者的基因型也可能影響TAC 的藥動學。過去TAC 藥動學研究多未合併研究臨床因素與基因因素，且基因研究僅針對單一基因。此外多數研究完全未考慮具交互作用藥品的影響，也缺乏臺灣人的研究。目的了解臺灣肝臟及腎臟器官移植病人各有哪些臨床因素（藥品交互作用、疾病、或臨床檢驗數值等）及基因多型性（ABCB1、CYP3A4、CYP3A5、POR 等）對於受贈者TAC 標準化谷濃度（dosenormalized trough concentration，dnC0）的影響。並希望了解過去臺灣未曾研究的肝臟捐贈者基因對肝臟受贈者TAC dnC0 的影響。方法本研究分為兩個部分，分別在腎臟移植病人及肝臟移植病人進行。將藉由臺大醫療體系醫療整合資料庫搜尋肝臟及腎臟移植的病人，分別分析肝臟移植及腎臟移植病人的臨床資料，分別找出各自顯著影響TAC dnC0 的臨床因素。並透過兩個族群各自SNP 檢測，合併臨床因素，利用多變項迴歸分析了解基因多型性的影響。在肝臟移植病人中也會檢測捐贈者的基因，納入分析。<br> Abstract: BackgroundTacrolimus (TAC) is the most important immunosuppressant for organ transplantation. Clinically, it isannoyed that the dose and concentration of TAC are difficult to adjust in some patients.Many clinical factors affect the pharmacokinetics (PK) of TAC. Literature suggests that ABCB1,CYP3A4, CYP3A5, POR gene polymorphisms may affect the PK of TAC, and have sufficient geneticfrequency in Asian. Because TAC is extensively metabolized in liver, its PK in liver transplant patientsmay also be influenced by genetic polymorphisms of donors.Most studies on TAC PK did not analyzed clinical and genetic factors concurrently, focused on onlyone gene, and did not examined concurrent medications that might have interactions. There also lacked ofstudy in Taiwanese.PurposeThe purpose of the study is to investigate the impact of clinical factors (drug interactions, diseases orlaboratory data, etc.) and genetic polymorphism (ABCB1, CYP3A4, CYP3A5, POR) on TAC dosenormalized trough concentration (dnC0) among Taiwanese liver and renal transplant patients. Theinfluence of genetic polymorphism of liver transplantation donors on recipients’ TAC dnC0 will also bestudied.MethodThis study has two parts. One will be conducted in kidney transplant patients, the other in livertransplant. We will use the electronic databases of National Taiwan University Hospital to identify patientswho underwent liver or renal transplantation, received TAC and were still followed up at the outpatientclinics. Databased will be used to identify factors that influences the TAC dnC0 in renal or livertransplantations, respectively. Single-nucleotide polymorphism (SNP) will be analyzed separately in thetwo different transplantations. Multivariate regression analysis will be used to analyze factors and geneticpolymorphism that influenced TAC dnC0 in renal and liver transplantation respectively. The geneticpolymorphisms of liver transplant donors will also be studied to understand their influence on recipients’TAC dnC0.Tacrolimus藥動學肝臟移植腎臟移植基因多型性臨床因素TacrolimusPharmacokineticsRenal transplantationLiver transplantationGenetic polymorphismClinical factors