Tacrolimus血中濃度之病人體內變異性及其對腎臟移植受贈者臨床治療的影響

Intra-Patient Variability of Tacrolimus Exposure and the Consequence for Clinical Management in Kidney Transplant Recipients

王慧瑜(Hue-Yu Wang) ； 田宇峰(Yu-Feng Tian) ； 孫定平(Ding-Ping Sun) ； 馮玉東(Yu-Tung Feng) ； 鄭景耀(Ching-Yao Cheng)

《臺灣臨床藥學雜誌》 29卷4期 (2021/10) Pp. 220-227

https://doi.org/10.6168/FJCP.202110_29(4).0004

摘要

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。

關鍵字

Tacrolimus ； 病人體內變異性（IPV） ； 藥物動力學 ； 依從性 ； 腎臟移植

並列摘要

Tacrolimus (FK506) is the drug of the top choice for immunosuppression in patients with a kidney transplant. FK506 adverse reactions such as hypertension, post-transplant 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.

並列關鍵字

Tacrolimus ； Intra-patient Variability (IPV) ； Pharmacokinetics ； Adherence ； Kidney Transplantation