Eljebari Hanene, Ben Fradj Nadia, Salouage Issam, Gaies Emna, Trabelsi Sameh, Jebabli Nadia, Lakhal Mohamed, Ben Othman Tarek, Kouz Anis
Laboratoire de Pharmacologie Clinique, Centre National de Pharmacovigilance, 9 Avenue Dr. Zouheïr Essafi, Tunis 1006, Tunisia.
J Transplant. 2012;2012:342701. doi: 10.1155/2012/342701. Epub 2011 Oct 26.
Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment in allogenic stem cell transplantation recipients to prevent graft-versus-host disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple linear regressions. All whole-blood samples were analyzed by fluorescence polarization immunoassay (FPIA-Axym). The 10 models that have used CsA concentrations at a single time point did not have a good fit with AUC(0-12) (R(2) < 0.90). C(2) and C(4) were the time points that correlated best with AUC(0-12 h), R(2) were respectively 0.848, and 0.897. The LSS equation with the best predictive performance (bias, precision and number of samples) utilized three sampling concentrations was AUC(0-12 h) = 0.607 + 1.569 × C(0.5) + 2.098 × C(2) + 3.603 × C(4) (R(2) = 0.943). Optimal LSSs equations which limited to those utilizing three timed concentrations taken within 4 hours post-dose developed from ASCT recipient's patients yielded a low bias <5% ranged from 1.27% to 2.68% and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model with equation AUC(0-12 h) = 0.82 + 2.766 × C(2) + 3.409 × C(4) for a practical reason. Bias and precision for this model are respectively 2.68% and 11.02%.
测量环孢素(CsA)的全身暴露量有助于在异基因干细胞移植受者中调整其剂量,以预防移植物抗宿主病。通过多元线性回归从60例异基因干细胞移植患者中建立并验证了CsA的群体药代动力学模型(LSSs)。所有全血样本均采用荧光偏振免疫分析法(FPIA-Axym)进行分析。使用单一时间点CsA浓度的10个模型与AUC(0-12)的拟合效果不佳(R(2) < 0.90)。C(2)和C(4)是与AUC(0-12 h)相关性最好的时间点,R(2)分别为0.848和0.897。具有最佳预测性能(偏差、精密度和样本数量)的LSS方程利用三个采样浓度,即AUC(0-12 h) = 0.607 + 1.569 × C(0.5) + 2.098 × C(2) + 3.603 × C(4)(R(2) = 0.943)。从异基因干细胞移植受者患者中得出的最佳LSSs方程限于那些使用给药后4小时内采集的三个定时浓度,其偏差较低<5%,范围为1.27%至2.68%,精密度良好<15%,范围为9.60%至11.02%。出于实际原因,我们提出了一个LSS模型,其方程为AUC(0-12 h) = 0.82 + 2.766 × C(2) + 3.409 × C(4)。该模型的偏差和精密度分别为2.68%和11.02%。