影響腎臟與肝臟移植病人tacrolimus血中濃度之因素

Factors Influencing the Blood Concentration of Tacrolimus in Kidney and Liver Transplant Patients

適當的免疫抑制治療對移植病人與移植器官存活率非常重要。Tacrolimus（TAC）是目前器官移植免疫抑制療法的骨幹，可用於心臟、肝臟、腎臟及其它實體器官移植，預防移植後的排斥反應。由於TAC療劑範圍（therapeutic range）狹窄，器官排斥與其副作用有時難以區隔，因此血中濃度的測定益發重要；但有許多因素會影響TAC的血中濃度，臨床上常發現同樣劑量在部分病人血中濃度超乎預期，劑量調整困難。本文回顧及彙整所有可能改變肝臟與腎臟移植病人tacrolimus吸收和清除的因素，目前已知臨床因素（包括年齡較大、男性、腎功能較差、肝功能較差、PTIINR較高、HBV帶原、HCV帶原、albumin及／或total protein較高、Hct及／或Hb較高、移植較久）會有較高的劑量校正後谷濃度（dnC_0）。CYP3A5的基因多 形性會顯著影響TAC的代謝，CYP3A5*3*3有較高的dnC_0；CYP3A4、ABCBl、POR的基因多形性在TAC藥動學上的影響則仍無定論。本文能協助臨床工作者詮釋TAC濃度與調整藥物治療，以達最佳效果。

Optimal immunosuppressive therapy is vital for patient and organ survival in solid organ transplantation. Currently, tacrolimus (TAC) is the backbone of immunosuppressive therapy in heart, kidney, liver, and other solid organ transplant to prevent post-transplant rejection. Because the therapeutic range of TAC is narrow, and some adverse effects of TAC may be difficult to differentiate from rejection, blood concentration monitoring is very important. However, TAC blood concentrations can be influenced by many factors. Clinically, blood concentrations in some patients are unexpectedly low or high at the usual dose, making the dosage adjustments difficult. This article reviewed all the reported factors that may change the absorption and clearance of TAC in liver and kidney transplant patients. Older age, male, poor renal function, poor liver functions, HBV carrier, HCV carrier, higher albumin and/or total protein, higher Hct and/or Hb, longer post-transplant days result in higher dosage normalized trough concentrations (dnC0). CYP3A5 genetic polymorphism has a significant effect on TAC metabolism. Patients with CYP3A5*3*3 have higher dnC_0. There is no conclusion on the influence of CYP3A4、ABCB1、POR genetic polymorphism on TAC metabolism. This review can help clinicians interpret the unexpected TAC concentration and modify drug therapy accordingly to achieve optimal outcomes