亲属活体供肝与儿童心脏死亡供肝儿童肝移植受者的他克莫司药动学分析

Pharmacokinetic analysis of tacrolimus in infants subject to living related liver transplantation and cardiac death liver transplantation

【摘要】目的探讨亲属活体供肝与儿童心脏死亡供肝儿童肝移植受者肝移植术后他克莫司的给药剂量、血药浓度和代谢特点。方法回顾性分析2012年10月至2015年8月期间75例患儿肝移植术后他克莫司的给药剂量、血药浓度、肝肾功能及排斥反应与感染的发生情况等临床资料，并将75例受者根据供者来源不同分组，其中亲属活体肝移植组（LRLT组）的受者40例，心脏死亡供者肝移植组（DI）LT组）的受者35例。结果（1）在两组受者他克莫司初始剂量相同情况下，术后1个月内DDLT组他克莫司给药剂量均较LRLT组略高，但差异无统计学意义（P〉0．05），而术后2个月和3个月时DDLT组的他克莫司给药剂量显著高于LRLT组（P=0．000）。（2）在相关性分析中，LRLT组移植物重量／受者体重（GRWR）与其术后第14天他克莫司剂量呈正相关（r=0．579，P〈0．05），与血他克莫司浓度／给药剂量值（Co／D）呈负相关关系（r=-0．657，P〈O．05）；DDLT组GRWR与术后第14天他克莫司剂量呈正相关关系（r：0．583，P〈0．05），与Co／D呈负相关关系（r=-0．607，P〈0．05）。结论婴幼儿肝移植术后应用他克莫司预防排斥反应的效果较好，但在不同受者间代谢差异较大。婴幼儿肝移植术后GRWR与他克莫司剂量呈正相关关系，在应用他克莫司时应根据其代谢特点及GIⅢR做适当的个体化调整。

Objective To analyze and compare the dosage, blood concentration and metabolic characteristics of Tacrolimus （Tac） for pediatric patients who underwent living related liver transplantation （LRLT） or donation after cardiac death liver transplantation （DDLT）. Methods The clinical data of 75 liver transplantation pediatric patients from October 2012 to August 2015 were retrospectively analyzed. According to the different source of donors, the recipients were divided into two groups： LRLT group （40 cases） and DDLT group （35 cases）. Results （I） Under the condition of same initial Tac dosage, the Tac dosage in LRLT group was less than in DDLT group during the first 28 days post-transplantation （P〉0. 05）. However, the Tac dosage in DDLT group was significantly higher than in LRLT group on the second and third months after sugery （P = 0. 000）. （2） Correlation analysis revealed that graft-recipient body weight ratio （GRWR） was correlated with Tac dosage （mg-kg-~ ＂d ~ ） on the 14th day postoperative （LRLT group： r= 0. 579, P〈0. 05; DDLT group： r= 0. 583, P〈0 05） and Tac concentration/dosage ratio （LRLT group： r = - 0. 607, P〈 0. 05; DDLT group： r = -0. 680, P〈0. 05）. Conehmion Tae has a satisfactory anti-rejection effect on liver transplantation pediatric patients while the metabolism varied with each individual. There is a positive correlation between the early Tac dosage and the GRWR in both groups. It is necessary to set individualized Tac administration regimen according to the metabolic characteristics and GRWR.