中国癫痫儿童丙戊酸钠群体药动学模型预测性能评估

Evaluation of the Prediction Performance of Population Pharmacokinetic Models of Sodium Valproate in Epileptic Children in China

目的回顾已发表的中国癫痫儿童丙戊酸钠群体药动学模型,通过外部验证评估其预测性能,为个体化给药提供参考。方法通过数据库检索已发表的中国癫痫儿童丙戊酸钠群体药动学模型,利用回顾性收集的患者信息进行外部验证,评价模型的预测能力。结果利用101例次血药浓度数据对检索到的4个中国癫痫儿童丙戊酸钠模型进行验证。结果显示,4个模型MPE、MAE、RMSE值相差不大,模型预测浓度与实测浓度拟合度好。Ding等建立的模型各区间预测误差符合率较好,对我院癫痫患儿更具针对性,但4个模型预测准确度差异不大。结论通过对4个模型预测性能的评估,模型B预测性能相对更好,但4个模型准确度整体差异不大。种族差异可能是影响模型准确度的重要因素,在后续研究中有待进一步探讨。

OBJECTIVE To compare all published sodium valproate population pharmacokinetic models of epileptic children in China and assess them by external validation to determine their predictive performance.METHODS The published population pharmacokinetic model of sodium valproate in children with epilepsy in China was collected by database retrieval.By retrospectively collecting patients’information,we performed an external validation to evaluate the power of prediction.RESULTS Four sodium valproate models were published before.The external validation of 101 samples showed that the MPE,MAE,RMSE of the four model were similar.All of them showed good adequacy between predicted concentrations and observed concentrations.Comparing with other models,the model established by Ding has better prediction error coincidence rate in most interval,which is more targeted for the prediction of individualized dosage regimen for epileptic children in our hospital.However,the overall prediction accuracy of the four models is not significantly different.CONCLUSION By the evaluation of four published population pharmacokinetic models of sodium valproate model B performs better than others,while the overall accuracy of the four models did not differ much.Racial difference may be an important factor affecting the accuracy of the model,which needs to be further explored in subsequent studies.