Kamińska Dorota, Poznański Paweł, Kuriata-Kordek Magdalena, Zielińska Dorota, Mazanowska Oktawia, Kościelska-Kasprzak Katarzyna, Krajewska Magdalena
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Transplant Proc. 2020 Oct;52(8):2288-2293. doi: 10.1016/j.transproceed.2020.02.109. Epub 2020 Apr 2.
The aim of the study was to assess bioavailability aspects of tacrolimus formulations during conversion from twice-daily (TAC BID) to once-daily (TAC OD) formulation in 89 stable kidney transplant recipients.
The study included 89 stable kidney transplant recipients transplanted between 1998 and 2008 (37 female, 52 male, aged 46.0 ± 12.4 years) and followed for 10 years. For a comprehensive comparison of the different tacrolimus formulations, dose-normalized trough levels (ng/mL/mg total daily dose, C/D ratio) and their variability were studied for 10 consecutive visits before and 6 months after conversion.
The mean trough level decreased significantly 14 days after conversion (16%, 5.77 ± 1.94 [5.6, 4.5-6.5] ng/mL, P < .001). There was no significant difference between the tacrolimus trough levels before and 3 months after conversion (6.92 ± 1.89 [6.8, 5.9-8.0] ng/mL, P = .548). The tacrolimus daily dose 3 months after conversion (4.56 ± 1.81 [4.5, 3.5-5.5] mg/d) was significantly higher than the dose before conversion (4.16 ± 1.80 [4.0, 3.0-5.0] mg/d, P = .006). The post-conversion mean TAC trough level (10 measures) (6.6 [6.2-7.0] ng/mL) was similar to preconversion level (6.8 [5.6-7.9] ng/mL, P = .203). C/D ratio as well as C/D intrapatient variability (CV%) did not change during conversion (C/D 1.68 [1.36-2.53] vs 1.74 [1.41 vs 2.31], P = .075; CV% 19.5 [16.4-26.6] vs 24.4 [17.5-28.3], P = .114).
Conversion from TAC BID to TAC OD is associated with a significant increase in tacrolimus dose during the first 3 months. In a long-term observation both formulations present similar dose-normalized trough levels and variability.
本研究旨在评估89例稳定的肾移植受者从他克莫司每日两次（TAC BID）制剂转换为每日一次（TAC OD）制剂过程中的生物利用度情况。
本研究纳入了89例在1998年至2008年期间接受肾移植的稳定受者（37例女性，52例男性，年龄46.0±12.4岁），随访10年。为全面比较不同的他克莫司制剂，在转换前连续10次就诊以及转换后6个月研究剂量标准化谷浓度（ng/mL/每日总剂量mg，C/D比值）及其变异性。
转换后14天平均谷浓度显著降低（16%，5.77±1.94[5.6,4.5 - 6.5]ng/mL，P <.001）。转换前与转换后3个月的他克莫司谷浓度无显著差异（6.92±1.89[6.8,5.9 - 8.0]ng/mL，P =.548）。转换后3个月的他克莫司每日剂量（4.56±1.81[4.5,3.5 - 5.5]mg/d）显著高于转换前的剂量（4.16±1.80[4.0,3.0 - 5.0]mg/d，P =.006）。转换后的他克莫司平均谷浓度（10次测量）（6.6[6.2 - 7.0]ng/mL）与转换前水平相似（6.8[5.6 - 7.9]ng/mL，P =.203）。转换过程中C/D比值以及患者内C/D变异性（CV%）未发生变化（C/D 1.68[1.36 - 2.53]对比1.74[1.41对比2.31]，P =.075；CV% 19.5[16.4 - 26.6]对比24.4[17.5 - 28.3]，P =.114）。
从TAC BID转换为TAC OD在最初3个月与他克莫司剂量显著增加相关。在长期观察中，两种制剂呈现相似的剂量标准化谷浓度和变异性。
