Hospital Pharmacy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Dept. of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
Pharm Res. 2021 Oct;38(10):1721-1729. doi: 10.1007/s11095-021-03115-8. Epub 2021 Oct 18.
Inaccurate documentation of sampling and infusion times is a potential source of error in personalizing busulfan doses using therapeutic drug monitoring (TDM). Planned times rather than the actual times for sampling and infusion time are often documented. Therefore, this study aimed to evaluate the robustness of a limited sampling TDM of busulfan with regard to inaccurate documentation.
A pharmacometric analysis was conducted in NONMEM® 7.4.3 and "R" by performing stochastic simulation and estimation with four, two and one sample(s) per patient on the basis of a one-compartment- (1CMT) and two-compartment (2CMT) population pharmacokinetic model. The dosing regimens consisted of i.v. busulfan (0.8 mg/kg) every 6 h (Q6H) or 3.2 mg/kg every 24 h (Q24H) with a 2 h- and 3 h infusion time, respectively. The relative prediction error (rPE) and relative root-mean-square error (rRmse) were calculated in order to determine the accuracy and precision of the individual AUC estimation.
A noticeable impact on the estimated AUC based on a 1CMT-model was only observed if uncertain documentation reached ± 30 min (1.60% for Q24H and 2.19% for Q6H). Calculated rPEs and rRmse for Q6H indicate a slightly lower level of accuracy and precision when compared to Q24H. Spread of rPE's and rRmse for the 2CMT-model were wider and higher compared to estimations based on a 1CMT-model.
The estimated AUC was not affected substantially by inaccurate documentation of sampling and infusion time. The calculated rPEs and rRmses of estimated AUC indicate robustness and reliability for TDM of busulfan, even in presence of erroneous records.
在使用治疗药物监测（TDM）为患者制定个体化的白消安剂量时，采样和输注时间记录不准确是一个潜在的误差源。通常记录的是计划时间，而不是实际的采样和输注时间。因此，本研究旨在评估有限采样白消安 TDM 对不准确记录的稳健性。
在 NONMEM® 7.4.3 和“R”中进行药代动力学分析，根据一个一室（1CMT）和两室（2CMT）群体药代动力学模型，对每个患者进行四次、两次和一次采样（s）的随机模拟和估计。给药方案包括静脉注射白消安（0.8mg/kg）每 6 小时（Q6H）或每 24 小时（Q24H）3.2mg/kg，分别输注 2 小时和 3 小时。计算相对预测误差（rPE）和相对均方根误差（rRmse），以确定个体 AUC 估计的准确性和精密度。
只有在文档记录不确定达到±30 分钟（Q24H 为 1.60%，Q6H 为 2.19%）时，1CMT 模型的 AUC 估计值才会受到明显影响。与 Q24H 相比，Q6H 的 rPE 和 rRmse 计算结果表明准确性和精密度略有降低。与基于 1CMT 模型的估计相比，2CMT 模型的 rPE 和 rRmse 的分布更宽，值更高。
采样和输注时间记录不准确不会显著影响 AUC 的估计。AUC 的 rPE 和 rRmse 计算值表明，即使存在错误记录，白消安 TDM 也具有稳健性和可靠性。
