Zhang Ren, Chen Ming, Liu Tao-Tao, Lu Jie-Jiu, Lv Chun-le
Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Eur J Drug Metab Pharmacokinet. 2020 Feb;45(1):135-149. doi: 10.1007/s13318-019-00578-4.
Most of the current published population pharmacokinetic (PopPK) models are based on serum creatinine, but we often encounter an underestimation of its concentration in our clinical work. Therefore, we established a cystatin C-based model of vancomycin.
The purpose of this study was to externally verify the PopPK model of vancomycin based on the glomerular filtration rate (GFR) estimated by serum cystatin C in our previous study and to compare the prediction performance of cystatin C (Cys C) and serum creatinine (SCR)-based models.
The external data set consists of adults receiving vancomycin treatment at The First Affiliated Hospital of Guangxi Medical University. We summarized and restored published models based on serum creatinine values from the literature and used our external data set for initial screening. Visual and external verifications were used to further select candidate models for comparison. The mean prediction error (ME), mean absolute error (MAE) and root mean squared error (RMSE) were the primary outcomes for the overall comparison. Group comparisons of patients with different glomerular filtration rates (GFRs), ages and body mass index (BMI) levels were obtained by the Bayesian method.
A total of 156 patients with 233 samples were collected as an external data set. Sixteen published models were summarized and restored. After screening, four candidate models suitable for the external data set were finally obtained for comparison. The cystatin C-based model has a smaller ME value in the overall comparison. In the group comparison, serum creatinine-based models were underestimated in the prediction for patient groups with age ≥ 60 years, abnormal BMI values and GFR < 90 ml/min/1.73 m, for which the cystatin C-based model could solve this problem.
After comparison, we suggest that cystatin C is a superior renal function marker to serum creatinine for vancomycin PopPK models.
目前大多数已发表的群体药代动力学（PopPK）模型是基于血清肌酐建立的，但在临床工作中我们经常遇到其浓度被低估的情况。因此，我们建立了基于胱抑素C的万古霉素模型。
本研究的目的是对外验证我们之前研究中基于血清胱抑素C估算的肾小球滤过率（GFR）建立的万古霉素PopPK模型，并比较基于胱抑素C（Cys C）和血清肌酐（SCR）的模型的预测性能。
外部数据集由在广西医科大学第一附属医院接受万古霉素治疗的成年人组成。我们根据文献中的血清肌酐值总结并还原已发表的模型，并使用我们的外部数据集进行初步筛选。通过可视化和外部验证进一步选择候选模型进行比较。平均预测误差（ME）、平均绝对误差（MAE）和均方根误差（RMSE）是总体比较的主要指标。通过贝叶斯方法对不同肾小球滤过率（GFR）、年龄和体重指数（BMI）水平的患者进行组间比较。
共收集156例患者的233份样本作为外部数据集。总结并还原了16个已发表的模型。经过筛选，最终获得4个适用于外部数据集的候选模型进行比较。在总体比较中，基于胱抑素C的模型的ME值较小。在组间比较中，基于血清肌酐的模型在预测年龄≥60岁、BMI值异常和GFR<90 ml/min/1.73 m²的患者组时被低估，而基于胱抑素C的模型可以解决这个问题。
经过比较，我们建议对于万古霉素PopPK模型，胱抑素C是比血清肌酐更好的肾功能标志物。
