Tacrolimus (FK506) 是目前腎臟移植免疫抑制方案的首選藥物。其獨特的不良反應如高血壓、移植後糖尿病、神經毒性與腎毒性等成為病人與移植體長期存活率的限制因素,在目前尚未有經核准且成功取代 FK506 之其他等效且毒性較小的免疫抑制劑之前,優化以 FK506 為主的免疫抑制方案至關重要。
FK506 藥物血中濃度之病人體內變異性 (intra-patient variability, FK-IPV),是指病人血中藥品濃度的波動率,此波動率與病人服藥順從性或干擾藥品吸收的因素有關;對腎臟移植者而言,FK-IPV 波動過高,可能引發急、慢性排斥反應或腎毒性的風險。過去對 FK-IPV 與腎臟移植預後相關性的研究認為,IPV 可做為預測腎臟移植預後的監測指標。
本文旨在回顧 FK506 IPV 與 FK506 藥物動力學之相關性及影響因素,概述其對長期器官移植預後之預測,提供降低 IPV 波動的介入方案與建議,以提升腎臟移植之醫療品質。
Tacrolimus (FK506) is the drug of the top choice for immunosuppression in patients with a kidney transplant. FK506 adverse reactions such as hypertension, posttransplant diabetes mellitus (PTDM), neurotoxicity, and nephrotoxicity, which reduce long-term graft survival. Attempts are unsuccessful in replacing Tac with other drugs, in terms of a less toxic immunosuppression. It is important to optimize Tac-based immunosuppressive regimens.
FK506 intra-patient variability (FK-IPV) refers to the fluctuation of FK506 blood levels within a given individual over a period of time. The rate of IPV fluctuation is likely due to the patient’s poor adherence or the interference on the FK506 absorption. For those kidney transplant recipients, a higher FK-IPV fluctuation may lead to acute or chronic rejection and the risk of nephrotoxicity. Previous studies on the correlation between FK-IPV and the prognosis of kidney transplantation believe that IPV can be used as a monitoring indicator to predict the prognosis of kidney transplantation. Herein, we aim to review the correlation and factors influencing IPV and pharmacokinetics of FK506, outlining long-term outcomes of kidney transplants, providing intervention programs and recommendations to reduce IPV for a higher quality of kidney transplantation.
Herein, we aim to review the correlation and factors influencing IPV and pharmacokinetics of FK506, outlining long-term outcomes of kidney transplants, providing intervention programs and recommendations to reduce IPV for a higher quality of kidney transplantation.
Summited for publication: 2021.3.15; Accepted for publication: 2021.6.1