Vondrak Karel, Dhawan Anil, Parisi Francesco, Grenda Ryszard, Debray Dominique, Marks Stephen D, Webb Nicholas J A, Lachaux Alain, Kazeem Gbenga, Undre Nasrullah
Department of Pediatrics, University Hospital Motol, Second School of Medicine, Charles University, Prague, Czech Republic.
Paediatric Liver GI and Nutrition Center, King's College Hospital, London, UK.
Pediatr Transplant. 2018 Dec;22(8):e13289. doi: 10.1111/petr.13289. Epub 2018 Oct 24.
Phase 2, parallel-group, multicenter, open-label, 4-week study, comparing PK of PR-T vs IR-T in de novo pediatric patients undergoing primary kidney, liver, or heart transplantation. Patients randomized 1:1 to receive once daily, PR-T-, or twice-daily, IR-T-based regimens; dose adjustments permitted after Day 1. Twenty-four-hour PK profiles collected on Days 1, 7, and 28. Primary endpoint: tacrolimus AUC . Secondary end points included tacrolimus C and C . Endpoints compared between PR-T and IR-T on Days 1, 7, and 28. Predefined similarity interval for CIs of LSM ratios: 80%-125%. PK analysis set comprised 33 patients (PR-T, n = 15; IR-T, n = 18). Overall, AUC and C were lower on Day 1 vs 7 and 28. Geometric LSM ratios of PR-T:IR-T on Days 1, 7, and 28 were 66.3%, 92.5%, 99.9%, respectively, for AUC ; 66.3%, 82.2%, 90.9% for C ; and 77.3%, 120.3%, 92.2% for C . AUC 90% CI within predefined similarity interval on Day 28; other 90% CIs fell outside. Linear relationship was similar between AUC and C , and between tacrolimus formulations, suggesting that the same therapeutic drug monitoring method can be used with both formulations in de novo pediatric allograft recipients.
一项为期4周的2期平行组多中心开放标签研究，比较初治儿科肾、肝或心脏移植患者中普罗布考（PR-T）与速释他克莫司（IR-T）的药代动力学。患者按1:1随机分组，接受每日一次的PR-T方案或每日两次的基于IR-T的方案；第1天后允许调整剂量。在第1、7和28天收集24小时药代动力学曲线。主要终点：他克莫司曲线下面积（AUC）。次要终点包括他克莫司谷浓度（C）和峰浓度（C）。在第1、7和28天比较PR-T和IR-T之间的终点。LSM比率置信区间的预定义相似性区间为80%-125%。药代动力学分析集包括33例患者（PR-T组，n = 15；IR-T组，n = 18）。总体而言，第1天的AUC和C低于第7天和第28天。第1、7和28天PR-T:IR-T的几何LSM比率，AUC分别为66.3%、92.5%、99.9%；C分别为66.3%、82.2%、90.9%；C分别为77.3%、120.3%、92.2%。第28天AUC的90%置信区间在预定义相似性区间内；其他90%置信区间落在区间外。AUC与C之间以及他克莫司制剂之间的线性关系相似，这表明在初治儿科同种异体移植受者中，两种制剂可使用相同的治疗药物监测方法。
