Vancomycin Population Pharmacokinetics And Dose Optimization In Patients With Neutropenia

Objective:Taking patients with neutropenia as the research object,we analyze the blood concentration of vancomycin used in patients with neutropenia and explore possible influencing factors.Establishing a population pharmacokinetic（PPK）model of vancomycin in patients with neutropenia and carrying out population pharmacokinetic/pharmacodynamics（PPK/PD）research to predict the dosing regimen.Methods:This study retrospectively collected the clinical indicators of the patients with neutropenia from May 2013 to May 2022 in The First Hospital Of Chinese Medical University.Spearman single factor analysis was used to analyze the correlation between clinical indicators and steady-state trough concentration(C_trough)using IBM SPSS 25.0software;Kruskal-Wallis H test was used for secondary variables andχ²test was used for categorical variables to compare plasma concentration among different groups.Ordered multiple Logistic regression analysis was used to predict the risk factors affecting vancomycin steady-state trough concentration.A nonlinear hybrid effect model was used to establish PPK model of vancomycin in the patients with neutropenia.The internal validation of the model was conducted using Bootstrap,Goodness of fit and Visual Predictive Check method.In addition,data from patients from June 2022 to April 2023will be collected as external validation.Monte Carlo simulation was used to provide recommendations for the application of vancomycin inpatients with neutropenia in the PPK/PD study.Result:A total of 109 patients with neutropenia were included after screening.The median age of the patients was 52 years old,the median body weight was 65 kg,and the population proportion of sub-therapeutic plasma concentration of vancomycin was 57.8%.The Logistic results showed that the plasma concentration of vancomycin was significantly correlated with creatinine clearance,albumin,total bilirubin and serum alkaline phosphatase.A one-compartment model was been used to establish a PPK model of vancomycin in patients with neutropenia.The model formula is CL=6.08×(CL_cr/102.67)^1.12L/h,V_d=181×(CL_cr/102.67)^0.665L.The internal validation and external validation of the model showed that the model had good stability and accuracy,and the administration scheme was provided according to the creatinine clearance rate.Conclusion:The plasma concentration in patients with neutropenia is not easy to meet the standards.In the case of the clinical application of vancomycin,clinical attention should be given to concentration of creatinine in patients with neutropenia.The combination of therapeutic drug monitoring to establish the neutropenia patients PPK model is helpful for the implementation of the individual treatment,and can reduce the incidence of treatment failure.