Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients
Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients
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DOI：
10.1046/j.1397-3142.2000.00000.x
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发表时间：
2001-04-01
影响因子：
1.3
通讯作者：
Fitzsimmons, WE
中科院分区：
文献类型：
--
作者：
MacFarlane, GD;Venkataramanan, R;Fitzsimmons, WE
他克莫司监测在成人中的临床效用已得到充分证明。本研究比较了他克莫司在美国四个中心的34例肝移植患者的儿科人群中的监测情况，以及在美国六个中心的111例成人人群中的监测情况。在移植后（Tx）12周内的规定时间间隔评价受试者（成人和儿童）的他克莫司谷浓度和12项额外的实验室化学检查。儿童患者和移植物12周存活率分别为91%和88%，而成人患者和移植物存活率分别为97%和93%。第1周时，儿科患者他克莫司的平均口服剂量为0.13 +/-0.1 mg/kg/天，第3周时增加至0.30 +/-0.3 mg/kg/天，并在研究的剩余时间内保持不变。这些剂量比成人使用的剂量高出两到三倍。相比之下，通过PRO-Trac（TM）II酶联免疫吸附试验（ELISA）测定的平均全血谷浓度从第1周的11.3 +/-5.1 ng/mL降至第12周的6.3 +/-3.7 ng/mL，与成人的谷浓度无显著差异。儿科受试者的临床终点（排斥反应、肾毒性、死亡、再治疗）的发生率和分布与成人受试者不同。达到任何终点的儿童受试者的总百分比为74%，而成人人群为54%。这些数据表明成人和儿童人群对他克莫司的反应存在一些差异。
The clinical utility of tacrolimus monitoring in adults has been well documented. The present study compared tacrolimus monitoring in a pediatric population of 34 liver transplant patients in four US centers with an adult population of 111 patients in six US centers. Subjects (adult and pediatric) were evaluated, at defined intervals over 12 weeks post-transplantation (Tx), for tacrolimus trough concentrations and 12 additional laboratory chemistries. Pediatric patient and graft survival for the 12 weeks were 91% and 88%, respectively, as compared to 97% and 93%, respectively, for the adult population. The mean oral dosage of tacrolimus for pediatric patients was 0.13 +/-0.1 mg/kg/day at week 1, increased to 0.30 +/-0.3 mg/kg/day by week 3 and remained constant for the remainder of the study. These dosages were two- to three-fold higher than the dosage used in the adult population. In contrast, the mean whole-blood trough concentration, as determined by PRO-Trac (TM) II enzyme-linked immunosorbent assay (ELISA), decreased from 11.3 +/-5.1 ng/mL at week 1 to 6.3 +/-3.7 ng/mL by week 12 and was not significantly different from the trough concentration in adults. The incidence and distribution of the clinical end-points for the pediatric subjects (rejection, nephrotoxicity, death, re-Tx) were different from those observed in adults. The total percentage of pediatric subjects reaching any end-point: was 74%, as compared to 54% in the adult population. These data indicate several differences between the adult and pediatric populations in their response to tacrolimus.