关键词: 中性粒细胞缺乏, 万古霉素, 群体药代动力学模型

Abstract: AIM: To establish a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases who developed neutropenia.  METHODS: Patients from department of hematology with neutropenia in our hospital were taken into oue study.The patients (n=77) were performed trough and peak serum concentration of vancomycin, and their clinical data and medication information were collected. The Nonlinear mixed effect modeling approach (NONMEM) was used to establish the PPK model of those patients and model assessment and validation was carried out. Goodneess of fit plots and visual predictive check plus Bootstrap approach were used to assess validate our model. RESULTS: The model was a two compartment model, the final formulas were: clearance rate CL=6.84×(BW/70)0.75×(CLCR/116)0.895 ×exp(η1), distribution volume of central ventricle V1=20.5×(BW/70)×exp(η2), transport rate Q=15.2×(BW/70)0.75×exp(η3), distribution volume of peripheral ventricle V2=50×(BW/70)×exp(η4), (BW was body weight, CLCR was creatinine clearance rate). Additionally 15 patients with neutropenia were included to conduct external validation, and it showed good stability and accuracy. CONCLUSION: The establishment of PPK model of vancomycin in patients with hematologic diseases who developed neutropenia is helpful to realize the individualized application of vancomycin in this population.

Key words: neutropenia, vancomycin, population pharmacokinetics (PPK) model