Morine Yuji, Shimada Mitsuo, Torii Mayumi, Imura Satoru, Ikegami Toru, Kanemura Hirohumi, Arakawa Yusuke, Hanaoka Jun, Kanamoto Mami, Nii Akira, Yamazaki Naoshi
Department of Surgery, Institute of Health Bioscience, University of Tokushima Graduate School, Tokushima, 770-8503, Japan.
Dig Dis Sci. 2009 Aug;54(8):1789-93. doi: 10.1007/s10620-008-0551-0. Epub 2008 Nov 12.
The optimal administration of immunosuppressants such as tacrolimus (Tac) for small-for-size (SFS) grafts, where the functional liver mass is small and must regenerate, has not been reported so far. The aim of this study is to clarify the characteristics of Tac metabolism according to liver volume. Seven-week-old male Wistar rats were randomly divided into three groups: (1) Tac administrated and 70% Hx group (Tac 70% Hx group), (2) Tac administrated and 90% Hx group (Tac 90% Hx group), and (3) vehicle administrated and 90% Hx group (control 90% Hx group). In both the Tac groups, Tac (0.3 mg/kg) was given daily for 3 days before operation, and daily after surgery until sacrifice (each time point; n = 5). The plasma concentration of Tac (trough level), as well as liver toxicity, were measured. The plasma concentration of Tac in the Tac 90% Hx group was significantly higher than in the Tac 70% Hx group from 24 to 72 h after operation. Furthermore, expression of CYP3AII mRNA was significantly lower in the Tac 90% Hx group than in the Tac 70% Hx group. Regarding the liver toxicity, there was no significant difference in both the Tac 90% Hx and the control 90% Hx groups. In this experimental study, the plasma concentration of Tac was dependent on the remnant liver volume. Therefore, special attention in regard to Tac administration should also be taken for patients with SFS grafts in living-donor liver transplantation (LDLT).
对于小体积移植物（SFS），即功能性肝体积较小且必须再生的情况，目前尚未见有关他克莫司（Tac）等免疫抑制剂最佳给药方式的报道。本研究旨在阐明根据肝脏体积Tac代谢的特征。将7周龄雄性Wistar大鼠随机分为三组：（1）给予Tac并进行70%肝切除的组（Tac 70% Hx组），（2）给予Tac并进行90%肝切除的组（Tac 90% Hx组），以及（3）给予赋形剂并进行90%肝切除的组（对照90% Hx组）。在两个Tac组中，于手术前3天每天给予Tac（0.3 mg/kg），术后每天给药直至处死（每个时间点；n = 5）。测定Tac的血浆浓度（谷浓度）以及肝脏毒性。术后24至72小时，Tac 90% Hx组的Tac血浆浓度显著高于Tac 70% Hx组。此外，Tac 90% Hx组中CYP3AII mRNA的表达显著低于Tac 70% Hx组。关于肝脏毒性，Tac 90% Hx组和对照90% Hx组均无显著差异。在本实验研究中，Tac的血浆浓度取决于残余肝脏体积。因此，对于活体肝移植（LDLT）中的SFS移植物患者，在Tac给药方面也应给予特别关注。
