Limited sampling strategy for simultaneous estimation of the area under the concentration-time curve of tacrolimus and mycophenolic acid in adult renal transplant recipients
Limited sampling strategy for simultaneous estimation of the area under the concentration-time curve of tacrolimus and mycophenolic acid in adult renal transplant recipients
复制标题
DOI：
10.1097/ftd.0b013e31815f5416
复制
发表时间：
2008-02-01
影响因子：
2.5
通讯作者：
Suzuki, Toshio
中科院分区：
文献类型：
--
作者：
Miura, Masatomo;Satoh, Shigeru;Suzuki, Toshio
本研究的目的是开发一个有限的采样策略，允许同时估计他克莫司和霉酚酸（MPA），前药霉酚酸酯的活性代谢产物的浓度-时间曲线下面积（AUC），使用少量的样本进行肾移植患者。入组了50例日本患者。在移植后第28天，于上午9：00和下午9：00，在他克莫司和吗替麦考酚酯给药前和给药后1、2、3、4、6、9和12小时收集样品。从这些定时浓度数据中获得的完整药代动力学曲线用于选择最佳采样时间。三个误差指数（百分比平均误差，百分比平均绝对误差，百分比相对均方误差）被用来评估预测偏差，准确度和精密度。在C-2 h-C-4 h-C-9 h三个时间点计算的MPA的AUC（0-12）预测值与MPA的实际AUC（0-12）最接近（r（2）= 0.877），在相同时间点计算的他克莫司的AUC（0-12）预测值与实际AUC具有良好的相关性（r（2）0.928）。当采用谷浓度（C-Oh）3个采样时间点和给药后4 h内的另外2个采样时间点时，C-0 h-C-2 h-C-4 h 3个采样时间点是估计AUC（0-12）、2他克莫司和MPA的最佳采样时间点AUC（0-12）= 7.04-C-o + 1.71.C-2 + 3.23.C-4 + 15.19，r（2）0.799，P < 0.001; AUC（0-12）= 0.26.C-o + 2.06.C-2 + 3.82.C-4 + 20.38，r（2）= 0.693，P < 0.001。使用C-0 h-C-2 h-C-4 h三个时间点的预测公式的百分比平均误差、百分比平均绝对误差和百分比相对均方误差分别为：他克莫司为-0.3%，8.8%和13.5%; MPA为2.9%，17.1%和21.5%。使用C-2 h-C-4 h-C-9 h的有限采样策略提供了对接受肾移植的患者中他克莫司和MPA的AUC（0-12）的最可靠和准确的同时估计。此外，建议使用C-0 h-C-2 h-C-4 h的有限采样策略，用于同时估计他克莫司和MPA的AUC（0-12），重点是在给药后4小时内采集的样本，用于临床权宜之计。
The aim of this study was to develop a limited sampling strategy to allow the simultaneous estimation of the area under the concentration-time curves (AUCs) of tacrolimus and mycophenolic acid (MPA), the active metabolite of the prodrug mycophenolate mofetil, using a small number of samples from patients undergoing renal transplantation. Fifty Japanese patients were enrolled. On day 28 after transplantation, samples were collected just before and 1, 2, 3, 4, 6, 9, and 12 hours after tacrolimus and mycophenolate mofetil administration at 9:00 Am and 9:00 Pm. The full pharmacokinetic profiles obtained from these timed concentration data were used to choose the best sampling times. Three error indices (percent mean error, percent mean absolute error, and percent relative mean square error) were used to evaluate the predictive bias, accuracy, and precision. The predicted AUC(0-12) of MPA calculated at the three time Points Of C-2h-C-4h-C-9h best approximated the actual AUC(0-12) of MPA (r(2) = 0.877), and the AUC(0-12) of tacrolimus calculated at the same time points predicted a good correlation with the actual AUC (r(2) 0.928). When the three sampling times of trough level (C-Oh) and two other points within 4 hours after administration were used, the three points of C-0h-C-2h-C-4h were the best points for estimation of the AUC(0-12),2 tacrolimus and MPA (AUC(0-12) = 7.04-C-o + 1.71.C-2 + 3.23.C-4 + 15.19, r(2) 0.799, P < 0.001 and AUC(0-12) = 0.26.C-o + 2.06.C-2 + 3.82.C-4 + 20.38, r(2) = 0.693, P < 0.001, respectively). The percent mean error, percent mean absolute error, and percent relative mean square error of the prediction formula using the three time Points Of C-0h-C-2h-C-4h were -0.3%, 8.8%, and 13.5% for tacrolimus and 2.9%, 17.1%, and 21.5% for MPA, respectively. A limited sampling strategy using C-2h-C-4h-C-9h provides the most reliable and accurate simultaneous estimation of the AUC(0-12) of tacrolimus and MPA in patients undergoing renal transplantation. In addition, a limited sampling strategy using C-0h-C-2h-C-4h is recommended for the simultaneous estimation of the AUC(0-12) of tacrolimus and MPA when focused on samples collected within 4 hours after administration for clinical expediency.