Division of Pediatric Nephrology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.
Department of Pharmaceutical Services, Ronald Reagan UCLA Medical Center, Los Angeles, California, USA.
Pediatr Transplant. 2023 May;27(3):e14480. doi: 10.1111/petr.14480. Epub 2023 Feb 2.
Envarsus XR® (LCPT), a once daily dosage formulation of tacrolimus, is an FDA-approved medication in adult renal transplant recipients (RTRs). There are limited data on its pharmacokinetics (PK) in adolescent RTRs. We report here the PK profile of LCPT in adolescent RTRs.
The dose of LCPT was determined using a dose conversion ratio targeting 0.7 relative to the total daily immediate-release tacrolimus (IR-Tac) dose. On day 7 after converting to LCPT, patients had an abbreviated PK assessment with sampling at: 0 h (pre-dose), 8-, and 12-h post-dose. The PK data analysis was performed using Bayesian estimators. Our results were compared to those of published adult PK data for LCPT and pediatric PK data for IR-Tac and extended release tacrolimus (ER-Tac) formulation (Advagraf).
PK data from three adolescent patients on LCPT were evaluated. The mean (±SD) area under the time-concentration curve (AUC) was 240 (±20.22) h*ng/mL. The mean T was 9.01 ± 2.12 h, and the % fluctuation was 77.71 ± 3.96%. The AUC, T , and % fluctuation were similar to reported results in adult patients taking LCPT. The AUC was higher and the T was longer than what has been reported in pediatric patients taking IR-Tac and ER-Tac. In addition, the LCPT group showed a lower % fluctuation than patients receiving ER-Tac.
The PK evaluation of LCPT in adolescent RTRs showed similar results to adults. Adolescents taking LCPT had a higher AUC, a more attenuated T , and a lower fluctuation than that seen with ER-Tac in pediatrics.
依维莫司 XR（LCPT）是一种每日一次的他克莫司制剂，已获得美国食品药品监督管理局（FDA）批准用于成人肾移植受者（RTR）。目前，关于其在青少年 RTR 中的药代动力学（PK）数据有限。我们在此报告 LCPT 在青少年 RTR 中的 PK 特征。
LCPT 的剂量是通过靶向与即时释放他克莫司（IR-Tac）总日剂量的 0.7 倍的剂量转换比来确定的。在转换为 LCPT 后第 7 天，患者进行了简化的 PK 评估，采样时间为：0 小时（用药前）、8 小时和 12 小时。PK 数据分析采用贝叶斯估计器进行。我们的结果与 LCPT 的已发表成人 PK 数据和 IR-Tac 及延长释放他克莫司（ER-Tac）制剂（Advagraf）的儿科 PK 数据进行了比较。
评估了三名接受 LCPT 治疗的青少年患者的 PK 数据。平均（±SD）时-浓度曲线下面积（AUC）为 240（±20.22）h*ng/mL。平均 T 为 9.01±2.12 小时，波动度为 77.71±3.96%。AUC、T 和波动度与接受 LCPT 治疗的成年患者的报告结果相似。AUC 较高，T 较长，与儿科患者接受 IR-Tac 和 ER-Tac 的报告结果不同。此外，LCPT 组的波动度低于接受 ER-Tac 的患者。
LCPT 在青少年 RTR 中的 PK 评估结果与成人相似。接受 LCPT 的青少年的 AUC 较高，T 更延长，波动度更低，与儿科患者接受 ER-Tac 的情况不同。
