模型引导的儿童万古霉素个体化用药程序的编制及临床应用  

Composition and Clinical Application of A Program of Model-Informed Individualized Administration of Vancomycin in Children

作　　者：王俊 刘茂昌 李思婵 聂刚 庹亚莉 汪洋[1] WANG Jun;LIU Maochang;LI Sichan;NIE Gang;TUO Yali;WANG Yang(Department of Pharmacy,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,China)

机构地区：[1]华中科技大学同济医学院附属武汉儿童医院药剂科,武汉430016

出　　处：《中国药学杂志》2024年第14期1347-1352,共6页Chinese Pharmaceutical Journal

基　　金：湖北省卫生健康科研基金项目资助(WJ2019F007)。

摘　　要：目的 应用模型引导的精准用药技术促进万古霉素(Vam)在儿科临床中的个体化治疗。方法 收集患儿用药后Vam血药浓度数据,通过文献检索和外部验证筛选出适用于中国儿童的Vam群体药动学(PPK)模型。将优选模型嵌入JPKD软件的用户自定义模块,建立基于贝叶斯最大后验概率法(MAPB)的个体化用药预测程序。应用该程序辅助临床为患儿提供个体化剂量调整服务。通过案例分析展示本研究编制的个体化用药程序应用效果。结果 本研究共收集了22名患儿的32个Vam血药浓度外部验证数据,患儿年龄中位数为6.04岁(44周~14.58岁)。程序预测浓度与实测浓度相比较,平均预测误差、平均绝对预测误差、平均预测误差平方分别为(0.098 4±0.141)(0.109±0.133) mg·L^(-1)、(0.029 0±0.087 2) mg^(2)·L^(-2),外部验证结果表明所选模型具有良好的预测性能,适用于本研究目标群体。4名患儿基于个体化用药辅助程序预测结果调整了Vam用药方案,有效提升了Vam的目标谷浓度和AUC_(24 h)达标情况,明显改善了临床症状和炎性指标,且无不良反应发生。结论 本研究通过自主编程建立了Vam个体化用药预测程序,并将该程序应用于临床实际病例,保障了患者抗感染治疗的有效性和安全性。OBJECTIVE To promote individualized mediaction of vancomycin in pediatric patients by model-informed precision dosing.METHODS The data of vancomycin serum concentration were collected,and the population pharmacokinetics model,which is suitable for Chinese children,was selected through literature search and external validation.The optimal model was embedded into the user-defined module of JPKD software,and a prediction program of individualized medication was established based on maximum a posteriori-Bayesian.This program was applied to individualized dose adjustment for pediatric patients.Case-based clinical practice was used to evaluate the application of this program.RESULTS A total of 32 vancomycin concentration data collected from 22 children with a median age of 6.04 years(44 weeks to 14.58 years) were used for external validation.Comparing the predicted concentration with the measured concentration,the mean prediction error,mean absolute prediction error and mean squared prediction error were(0.098 4±0.141)(0.109±0.133) mg·L~(-1) and(0.029 0±0.087 2) mg~2·L~(-2),respectively.The results of external validation showed that the selected model had an acceptable predictive performance and was appropriate for the target group in this study.Dosing regimens of vancomycin were adjusted for four pediatric patients based on the predicted results of individualized adjuvant medication program,which led to an effectively improved target attainment situation of vancomycin trough concentration and AUC_(24 h),significantly convalescent clinical symptoms and inflammatory indicators,while no adverse reactions occurred.CONCLUSION In the current study,a prediction program for individualized medication of vancomycin is successfully established by independent programming and applied to clinical cases.It guarantees the effectiveness and safety of anti-infective therapy for patients.

关 键 词：万古霉素 模型引导的精准用药 儿童 个体化治疗 临床应用 

分 类 号：R969[医药卫生—药理学]