中国成年患者万古霉素群体药动学研究

目的:利用万古霉素治疗药物监测(TDM)数据建立群体药动学(PPK)模型,用于估算个体化药动学参数。方法:选择使用万古霉素成年患者,详细记录用药、TDM数据以及病理生理资料。采用非线性混合效应模型(NONMEM)法建立万古霉素群体药动学模型。结果:169例患者数据来源于血液科及重症监护(ICU)病房等9个科室,共获得385个血药浓度数据,其中峰浓度39个,谷浓度346个。根据文献资料及TDM数据建立二室PPK模型,万古霉素清除率(CL)、中央室(V1)及外周室(V2)分布容积、室间清除率分别为4.08 L·h-1、21.7 L、65.3 L、5.95 L·h-1,患者肌酐清除率及体重分别对CL及V2具有显著影响。根据模型预测169位患者AUC0-24h为(450.1±231.8)mg·L-1·h。结论:本研究建立的万古霉素PPK模型可以用于中国成年患者个体化药动学参数估算。

Population Pharmacokinetics Model of Vancomycin in Chinese Adult Patients

Objective: To establish a population pharmacokinetics (PPK) model of vacomycin based on the therapeutic drug monitoring (TDM) data. The individualized pharmacokinetic parameters of vancomycin can be estimated through the model. Methods: The adult patients treated with vacomycin were recruited. Data of dosage regimen, plasma concentration, physiological and pathological condition were collected. The Nonlinear Mixed Effect Model (NONMEM) was used to establish the vancomycin PPK model. Results: Data of 169 patients from 9 departments including hematology and intensive care unit were collected, 385 samples of vancomycin plasma concentrations including 39 peak and 346 trough concentrations were obtained. A two-compartment model was established based on the data from references and TDM data. The clearence (CL), volume distribuation of cetranl (V₁) and peripheral compartment (V₂), intercompartmental clearence (Q) of base model were estimated as 4.28 L·h^-1, 1.25 L, 39.9 L and 9.78 L·h^-1, respectively. The clearance of creatinine (CLcr) and body weight were found to have significant impact on CL and V₂, respectively. According to the PPK model established, the AUC_0-24 of 169 patients were (450.01±231.8) mg·L^-1·h. Conclusion: The PPK model we established can be used to estimate the individualized vancomycin pharmacokinetic parameters in Chinese adult patients.