Lapeyraque Anne-Laure, Kassir Nastya, Théorêt Yves, Krajinovic Maja, Clermont Marie-José, Litalien Catherine, Phan Véronique
Service de Néphrologie, Département de Pédiatrie, CHU de Sainte-Justine, Université de Montréal, Montréal, Canada,
Pediatr Nephrol. 2014 Jun;29(6):1081-8. doi: 10.1007/s00467-013-2724-0. Epub 2014 Jan 17.
The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients.
Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7-19 years). Tacrolimus pharmacokinetic parameters [area under the concentration-time curve (AUC0-24), minimum whole-blood concentration (Cmin), maximum whole-blood concentration (Cmax), and time to achieve maximum whole-blood concentration (tmax)] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization.
Both AUC0-24 and Cmin decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p = 0.03 and 0.01, respectively). However, the ratio of the least square means (LSM) for AUC0-24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized Cmin with the twice-daily formulation only.
Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC0-24 and Cmin after the conversion, requiring close pharmacokinetic monitoring during the conversion period.
本研究的目的是调查儿科肾移植受者从每日两次（普乐可复）他克莫司制剂以1:1（毫克:毫克）的比例转换为每日一次（新普乐可复）他克莫司制剂过程中的药代动力学和药物遗传学参数。
对19名稳定的肾移植受者（年龄7 - 19岁）转换前后的24小时药代动力学曲线进行分析。在剂量标准化后，比较他克莫司制剂之间以及CYP3A5和MDR1基因型之间的他克莫司药代动力学参数[浓度 - 时间曲线下面积（AUC0 - 24）、最低全血浓度（Cmin）、最高全血浓度（Cmax）以及达到最高全血浓度的时间（tmax）]。
转换后AUC0 - 24和Cmin均下降（分别从223.3降至197.5 ng·h/ml和从6.5降至5.6 ng/ml；p分别为0.03和0.01）。然而，AUC0 - 24的最小二乘均值（LSM）比值为90.8%，90%置信区间为85.3%至96.7%，处于生物等效性范围内。仅每日两次制剂的CYP3A5基因型会影响剂量标准化后的Cmin。
两种他克莫司制剂在儿科肾移植受者中具有生物等效性。然而，我们观察到转换后AUC0 - 24和Cmin下降，在转换期间需要密切进行药代动力学监测。
