中国老年患者万古霉素群体药动学及个体化给药应用研究

Population pharmacokinetics of vancomycin in Chinese elderly patients and its application for dose individualisation

本研究旨在构建中国老年患者万古霉素群体药动学(population pharmacokinetics, PPK)模型,为中国老年患者提供个体化给药方案。前瞻性收集使用万古霉素的中国老年患者数据,采用酶联免疫分析法检测万古霉素稳态血药浓度,记录患者性别、年龄、体重、合并用药、感染类型以及实验室检查指标等信息。NONMEM(nonlinearmixed-effectsmodel)软件构建PPK模型,蒙特卡洛模拟法设计老年患者的万古霉素初始给药剂量表。研究发现开颅术后脑膜炎与肾小球滤过率是影响万古霉素清除率的主要协变量;并设计了万古霉素在老年开颅术后脑膜炎及非开颅术后脑膜炎患者中的初始给药剂量推荐表。本研究最终建立了能估算中国老年患者万古霉素个体清除率的PPK模型,为老年患者万古霉素的个体化给药提供参考。

In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findings were recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance(CL) was significantly influenced by post-craniotomy meningitis(PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.