Department of Pharmacy, Akita University Hospital, Akita, Japan.
Ther Drug Monit. 2013 Apr;35(2):228-32. doi: 10.1097/FTD.0b013e31827efe37.
The aim of this study was to develop a limited sampling strategy to estimate the area under the concentration-time curve (AUC) of a modified-release, once-daily formulation of tacrolimus (Advagraf, Japanese trade name Graceptor) with Japanese renal transplant patients.
Among the 43 enrolled patients, 23 patients continued to take Graceptor for 1 year. A total of 66 profiles on day 28 and day 365 from the 43 patients were randomly divided into a training group (N = 33) and a validation group (N = 33) without any overlap.
The prediction formula for the AUC 0-24 using the single C 12h time point gave the highest correlation with the observed AUC 0-24 (r2 = 0.9057). When 2 sampling times were used, C 0h-C 12h were the best time points for the estimation of the AUC 0-24 (AUC 0-24 = 26.8 + 8.0C 0h + 17.8C 12h, r2 = 0.9221, P < 0.0001). There was no significant difference in the prediction error for the prediction formulas with the C 0h-C 12h combination between CYP3A5 genotypes. The % mean prediction error, % mean absolute error, and % root mean squared prediction error of the prediction formula using C 0h-C 12h were 0.1%, 7.6%, and 8.8%, respectively.
In a hospital setting, a limited sampling strategy using C 0h-C 12h would be applicable to estimating the AUC 0-24 of tacrolimus once daily.
本研究旨在为接受他克莫司（Advagraf，日本商品名 Graceptor）改良型、每日 1 次缓释制剂的日本肾移植患者建立一种估算浓度-时间曲线下面积（AUC）的有限采样策略。
在 43 名入组患者中，23 名患者继续服用 Graceptor 1 年。对这 43 名患者中的 66 例在第 28 天和第 365 天的血药浓度数据，无重叠随机分为训练组（n = 33）和验证组（n = 33）。
单点 C 12h 时间点预测 AUC 0-24 的公式与观察的 AUC 0-24 相关性最高（r2 = 0.9057）。当使用 2 个采样点时，C 0h-C 12h 是估算 AUC 0-24 的最佳时间点（AUC 0-24 = 26.8 + 8.0C 0h + 17.8C 12h，r2 = 0.9221，P < 0.0001）。C 0h-C 12h 组合的预测公式在 CYP3A5 基因型之间的预测误差没有显著差异。使用 C 0h-C 12h 的预测公式的%平均预测误差、%平均绝对误差和%均方根预测误差分别为 0.1%、7.6%和 8.8%。
在医院环境中，使用 C 0h-C 12h 的有限采样策略可能适用于估算他克莫司每日 1 次的 AUC 0-24。
