Webb Nicholas J A, Baumann Ulrich, Camino Manuela, Frauca Esteban, Undre Nasrullah
Department of Paediatric Nephrology and NIHR/Wellcome Trust Manchester Clinical Research Facility, University of Manchester, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Manchester, UK.
Division of Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany.
Pediatr Transplant. 2019 Feb;23(1):e13328. doi: 10.1111/petr.13328. Epub 2019 Jan 21.
Tacrolimus granules were developed for patients who are unable to swallow capsules. Therapeutic drug monitoring (TDM) is required to optimize efficacy and safety, which is based on C for tacrolimus capsules. Pharmacokinetic (PK) data for tacrolimus granules are required to establish the basis for TDM in those who are unable to swallow capsules. In this phase IV study (NCT01371331) of children undergoing liver, kidney, or heart transplantation, patients received tacrolimus granules 0.15 mg/kg twice daily; first dose was administered within 24 hours of reperfusion. PK analysis samples were collected after reperfusion, after first dose of tacrolimus (Day 1), and at steady state (Day 7; >4 days stable dose). Of the 52 transplant recipients enrolled, 38 had two evaluable PK profiles. Mean AUC after first dose of tacrolimus was 211, 97, and 224 hourng/mL in liver, kidney, and heart transplant recipients, respectively; corresponding mean AUC at steady state was 195, 208, and 165 hourng/mL. C and AUC were positively correlated after first dose of tacrolimus and at steady state (Pearson's coefficients: r = 0.81 and r = 0.87, respectively). This study demonstrated that C is a reliable marker for TDM in pediatric transplant recipients treated with tacrolimus granules, consistent with TDM for other tacrolimus formulations.
他克莫司颗粒剂是为无法吞咽胶囊的患者研制的。为优化疗效和安全性，需要进行治疗药物监测（TDM），其基于他克莫司胶囊的血药浓度（C）。需要他克莫司颗粒剂的药代动力学（PK）数据，以便为无法吞咽胶囊的患者建立TDM的依据。在这项针对接受肝、肾或心脏移植的儿童的IV期研究（NCT01371331）中，患者接受每日两次0.15mg/kg的他克莫司颗粒剂；首剂在再灌注后24小时内给药。在再灌注后、他克莫司首剂给药后（第1天）以及稳态时（第7天；稳定剂量>4天）采集PK分析样本。在登记的52名移植受者中，38名有两个可评估的PK曲线。肝、肾和心脏移植受者在他克莫司首剂给药后的平均血药浓度-时间曲线下面积（AUC）分别为211、97和224小时纳克/毫升；稳态时相应的平均AUC分别为195、208和165小时纳克/毫升。在他克莫司首剂给药后和稳态时，血药浓度（C）与AUC呈正相关（Pearson系数：分别为r = 0.81和r = 0.87）。本研究表明，在接受他克莫司颗粒剂治疗的儿科移植受者中，血药浓度（C）是TDM的可靠标志物，这与其他他克莫司制剂的TDM一致。
