Heffron T G, Pescovitz M D, Florman S, Kalayoglu M, Emre S, Smallwood G, Wisemandle K, Anania C, Dhadda S, Sawamoto T, Keirns J, Fitzsimmons W, First M R
Emory University School of Medicine, Atlanta, GA, USA.
Am J Transplant. 2007 Jun;7(6):1609-15. doi: 10.1111/j.1600-6143.2007.01803.x.
The pharmacokinetics, safety and tolerability of a once-daily formulation of tacrolimus (tacrolimus extended-release formulation; XL formerly referred to as MR or MR4) were assessed in 18 stable pediatric liver transplant recipients who were converted from the twice-a-day formulation of tacrolimus (TAC) to XL. Patients received their twice-a-day dose of TAC on study days 1 through 7. Beginning on the morning of study day 8, patients were converted to XL on a 1:1 (mg:mg) basis for their total daily dose, and were maintained on a once-daily AM dosing regimen using the same therapeutic monitoring and patient care techniques employed with TAC. Based on pharmacokinetic profiles obtained on study days 7 (TAC) and 14 (XL), steady state exposure (AUC(0-24)) was equivalent between XL and TAC; the mean XL/TAC ratio for lnAUC(0-24) was 100.9% (90% CI: 90.8%, 112.1%). AUC(0-24) and C(min) were strongly correlated at steady state (correlation coefficient: XL 0.90, TAC 0.94). During the first year post-conversion, there were no cases of acute rejection, discontinuation of XL, graft loss or death. The safety profile of XL was consistent with that known for TAC. These results support the safe and convenient conversion of pediatric liver transplant recipients from twice-a-day TAC to once-daily XL.
在18例稳定的小儿肝移植受者中评估了他克莫司每日一次剂型（他克莫司缓释制剂；XL，以前称为MR或MR4）的药代动力学、安全性和耐受性，这些受者从他克莫司（TAC）每日两次剂型转换为XL。患者在研究第1天至第7天接受每日两次剂量的TAC。从研究第8天上午开始，患者按每日总剂量1:1（mg:mg）转换为XL，并采用与TAC相同的治疗监测和患者护理技术，维持每日一次上午给药方案。根据在研究第7天（TAC）和第14天（XL）获得的药代动力学曲线，XL和TAC之间的稳态暴露量（AUC(0-24)）相当；lnAUC(0-24)的平均XL/TAC比值为100.9%（90%CI：90.8%，112.1%）。AUC(0-24)和C(min)在稳态时高度相关（相关系数：XL为0.90，TAC为0.94）。在转换后的第一年，没有急性排斥反应、停用XL、移植物丢失或死亡的病例。XL的安全性与已知的TAC安全性一致。这些结果支持小儿肝移植受者从每日两次TAC安全、方便地转换为每日一次XL。
