Carcas-Sansuán Antonio J, Espinosa-Román Laura, Almeida-Paulo Gonzalo N, Alonso-Melgar Angel, García-Meseguer Carmen, Fernández-Camblor Carlota, Medrano Nicolás, Ramirez Elena
Clinical Pharmacology Service, University Hospital La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain,
Pediatr Nephrol. 2014 Jan;29(1):117-23. doi: 10.1007/s00467-013-2564-y. Epub 2013 Aug 2.
The conversion from Prograf to Advagraf on a 1:1 (mg:mg) basis has been questioned in light of the publication of studies showing a decrease in tacrolimus blood concentrations after the administration of Advagraf.
The bioavailability of Prograf and Advagraf was evaluated in an open-label conversion study in 21 stable renal transplant paediatric patients. Serial blood samples for determining tacrolimus levels were collected during a 24-h period before (on Prograf) and after (on Advagraf) conversion. Tacrolimus pharmacokinetic parameters were calculated using a non-compartmental approach and the relative bioavailability calculated. Clinical and analytical data were obtained at 30, 90, 180 and 360 days after study enrolment.
The mean ratio and 90 % confidence interval (CI) for peak plasma drug concentration (C(max)) and the area under the time-concentration curve during the first 24 h (AUC(0-24)) were 81.54 (95 % CI 71.6-92.87) and 87.19 (95 % CI 79.91-95.13), respectively. Renal glomerular filtration rate remained stable over the course of the follow-up. Two patients presented clinical events unrelated to tacrolimus. Tacrolimus levels decreased in the first month, the dose/level ratio increased between months 1 and 6 and slight dose adjustments were required during the follow-up period.
Our results show that Advagraf bioequivalence cannot be ensured in this population. Significant changes in tacrolimus levels and dose were observed on long-term follow-up.
鉴于有研究表明使用新山地明（Advagraf）后他克莫司血药浓度降低，1:1（毫克:毫克）剂量从普乐可复（Prograf）转换为新山地明受到质疑。
在一项开放标签转换研究中，对21例稳定的肾移植儿科患者评估了普乐可复和新山地明的生物利用度。在转换前（服用普乐可复时）和转换后（服用新山地明时）的24小时内采集系列血样以测定他克莫司水平。采用非房室方法计算他克莫司药代动力学参数并计算相对生物利用度。在研究入组后30、90、180和360天获取临床和分析数据。
血浆药物峰浓度（C(max)）和给药后最初24小时的时间-浓度曲线下面积（AUC(0-24)）的平均比值及90%置信区间（CI）分别为81.54（95%CI 71.6 - 92.87）和87.19（95%CI 79.91 - 95.13）。随访期间肾小球滤过率保持稳定。两名患者出现与他克莫司无关的临床事件。他克莫司水平在第一个月下降，剂量/水平比值在第1至6个月增加，随访期间需要进行轻微的剂量调整。
我们的结果表明，在该人群中不能确保新山地明的生物等效性。长期随访中观察到他克莫司水平和剂量有显著变化。
