Wang Genzhu, Sun Qiang, Li Xiaojing, Mei Shenghui, Li Shihui, Li Zhongdong
Electric Power Teaching Hospital, Capital Medical University, Beijing, 100073, China.
Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Curr Drug Metab. 2024;25(7):479-488. doi: 10.2174/0113892002322494240816032948.
Various population pharmacokinetic (PPK) models have been established to help determine the appropriate dosage of docetaxel, however, no clear consensus on optimal dosing has been achieved. The purpose of this study is to perform an external evaluation of published models in order to test their predictive performance, and to find an appropriate PPK model for Chinese breast cancer patients.
A systematic literature search of docetaxel PPK models was performed using PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases. The predictive performance of eleven identified models was evaluated using prediction-based and simulation-based diagnostics on an independent dataset (112 docetaxel concentrations from 56 breast cancer patients). The -2×log (likelihood) and Akaike information criterion were also calculated to evaluate model fit.
The median prediction error of eight of the eleven models was less than 10%. The model fitting results showed that the three-compartment model of Bruno et al. had the best prediction performance and that the three compartment model of Wang et al. had the best simulation effect. Furthermore, although the covariates that significantly affect PK parameters were different between them, seven models demonstrated that docetaxel PK parameters were influenced by liver function.
Three compartment PPK models may be predictive of optimal docetaxel dosage for Chinese breast cancer patients. However, for patients with impaired liver function, the choice of which model to use to predict the blood concentration of docetaxel still requires great care.
已建立多种群体药代动力学（PPK）模型以帮助确定多西他赛的合适剂量，然而，在最佳给药方案上尚未达成明确共识。本研究的目的是对已发表的模型进行外部评估，以测试其预测性能，并为中国乳腺癌患者找到合适的PPK模型。
使用PubMed、Web of Science、中国知网和万方数据库对多西他赛PPK模型进行系统的文献检索。使用基于预测和基于模拟的诊断方法，在一个独立数据集（来自56例乳腺癌患者的112个多西他赛浓度）上评估11个已识别模型的预测性能。还计算了-2×对数（似然值）和赤池信息准则以评估模型拟合情况。
11个模型中有8个的中位预测误差小于10%。模型拟合结果表明，Bruno等人的三室模型具有最佳预测性能，而Wang等人的三室模型具有最佳模拟效果。此外，尽管它们之间显著影响药代动力学参数的协变量不同，但7个模型表明多西他赛药代动力学参数受肝功能影响。
三室PPK模型可能有助于预测中国乳腺癌患者的多西他赛最佳剂量。然而，对于肝功能受损的患者，选择使用哪种模型来预测多西他赛血药浓度仍需谨慎。
