Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Transplantation. 2011 Sep 27;92(6):648-52. doi: 10.1097/TP.0b013e3182292426.
Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation.
The aim of this study is to prospectively investigate the change of within-patient variability among stable kidney transplant recipients with conversion from twice-daily Prograf to the same milligram-for-milligram daily dose of once-daily Advagraf.
The mean age of 129 patients was 51.3±12.1 years. The conversion to Advagraf was administrated at 6.3±4.8 years after transplantation. The daily dose was changed from 4.7±2.0 mg to 4.9±2.1 mg after conversion. Only six patients increased daily dose by 16.7% to 25% to maintain target levels. The whole blood C0 of tacrolimus before conversion was 5.9±1.7 ng/mL. The mean C0 was significantly reduced after conversion to Advagraf; it was 4.9±1.5 ng/mL on the seventh day (P<0.001) and 5.4 to 5.5 ng/mL at 1 to 6 months (P<0.05). Forty-one (31.8%) patients have reduced C0 of more than 25% on the seventh day. The percent coefficient of variation of tacrolimus C0 more than 22.5% before conversion is associated with higher risk of reduced C0 after conversion (P<0.05). Compared with before conversion, less kidney transplant recipients have percent coefficient of variation more than 22.5% after conversion (3.1% vs. 17.4% with P<0.01).
The results support that conversion from Prograf to Advagraf among kidney transplant recipient leads to a significantly lower C0 and within-patient variability of tacrolimus C0. The within-patient variability of C0 before conversion influences C0 on the sevent day after conversion to Advagraf.
免疫抑制剂血药谷浓度(C0)的变异性导致肾移植后排斥反应和移植物丢失。
本研究旨在前瞻性研究将两次/日普乐可复转换为相同毫克/毫克剂量的一次/日他克莫司的稳定肾移植受者中患者内变异性的变化。
129 例患者的平均年龄为 51.3±12.1 岁。转换为他克莫司的时间为移植后 6.3±4.8 年。转换后,每日剂量从 4.7±2.0mg 变为 4.9±2.1mg。只有 6 名患者将每日剂量增加 16.7%至 25%以维持目标水平。转换前他克莫司全血 C0 为 5.9±1.7ng/ml。转换为他克莫司后 C0 均值显著降低;第 7 天为 4.9±1.5ng/ml(P<0.001),1 至 6 个月为 5.4 至 5.5ng/ml(P<0.05)。41 例(31.8%)患者在第 7 天 C0 降低超过 25%。转换前他克莫司 C0 的变异系数超过 22.5%与转换后 C0 降低的风险较高相关(P<0.05)。与转换前相比,转换后他克莫司 C0 的变异系数超过 22.5%的肾移植受者较少(3.1%比 17.4%,P<0.01)。
结果支持肾移植受者将普乐可复转换为他克莫司后,他克莫司 C0 的血药谷浓度和患者内变异性显著降低。转换前 C0 的患者内变异性影响转换为他克莫司后第 7 天的 C0。