基于群体药动学的拉莫三嗪个体化剂量调整研究

Study on Individualized Dosage Adjustment of Lamotrigine Based on Population Pharmacokinetics

目的:基于群体药动学方法,预测患者不同用药方案服用拉莫三嗪后的稳态血药浓度,为临床治疗提供参考。方法:收集58例患者的282个拉莫三嗪血药浓度观测值,并记录联合应用丙戊酸的情况,利用已经建立的拉莫三嗪群体药动力学模型,分别通过第1个、前2个血药浓度值估算个体间变异,并预测后续浓度值,评估两种情况对模型预测准确性的影响。结果:预测结果显示,分别采用第1个、前2个血药浓度值预测产生的误差的中位值分别为-0.32、-0.41μg/ml,均接近0值;得到的平均预测误差分别为-0.66、-0.42μg/ml,均方根误差分别为3.80、3.19μg/ml,说明在上述两种情况下,模型均有较好的预测性。结论:无论从采集1个浓度值还是2个浓度值时开始使用该模型进行预测,均能得到较准确的预测结果。

OBJECTIVE： Based on population pharmacokinetics,to predict the steady-state plasma concentrations of lamotrigine（ LTG） in patients with different drug regimens and provide reference for clinical treatment. METHODS：58 patients were enrolled, with 282 LTG concentrations and corresponding comedication of VPA records. An established population pharmacokinetic model was applied to predict the following up concentrations of LTG based on the inter-subject variabilities estimated from the first observation in each patient or the first two observations in each patient. The precision and accuracy of the prediction were evaluated under the two scenarios. RESULTS： According to prediction results,the median prediction errors of the two scenarios were respectively -0. 32 μg/ml and -0. 41 μg/ml,which were close to zero; the mean prediction error（ MPE） were -0. 66 μg/ml and -0. 42 μg/ml,and root mean squared error（ RMSE） were 3. 80 μg/ml and 3. 19 μg/ml,respectively. Thus,the model exhibited good prediction efficiency under both scenarios. CONCLUSIONS： The results demonstrated that no matter based on one or two observations,the model would both show accurate prediction.