| Objective:To establish a method of high performance liquid chromatography for the determination of serum concentration of vancomycin in pediatric patients in our hospital;to summarize and analyze the distribution and compliance of the blood vancomycin concentration of pediatrics;to explore the rationality of the target vancomycin concentration in our pediatric diagnosis and treatment center through the effectiveness and safety of clinical effectiveness;to perform therapeutic drug monitoring?TDM?of vancomycin in our hospital for pediatrics;to ensure the safety and effectiveness of vancomycin application in pediatrics,we wanted to develop a new suitable TDM and individualized administration mode of vancomycin in pediatrics,so as to ensure the effectiveness and safety of vancomycin in the clinical application in pediatric in our hospital.Methods:The serum concentration of vancomycin was determined by HPLC method.The information of pediatrics who accepted TDM in the pediatric diagnosis and treatment center from January 2018 to January 2020 was collected,and the distribution and compliance of blood vancomycin concentration were statistically analyzed.The therapeutic efficacy and safety evaluation and pharmaceutical care were conducted on all pediatrics in this study,and the rationality of the target concentration of vancomycin in the pediatric treatment center of our hospital was analyzed and discussed.A suitable Chinese pediatric vancomycin population pharmacokinetic model was selected,and individualized drug administration design and prediction were carried out for pediatric patients by combining with the based pharmacokinetic prediction software"JPKD"and the Bayesian feedback method,and the newly established new vancomycin TDM and individualized drug administration mode were evaluated methodologically and verified by clinical examples.Result:The linearity of vancomycin serum concentration in pediatrics was good in the range of 5-100mg·ml-1.The regression equation is:y=3991.321x-7333.622,r=0.999,the detection limit is 1.5?g·ml-1,and the lower limit of quantification is 5?g·ml-1,retention time is 25.2min,peak shape is complete with no interference of spurious peaks,both intra-day precision and inter-day precision RSD<10%,recovery rate is between 100%-105%,The sample of concentration>10?g·ml-11 has good room-temperature stability within 24 hours,RSD<20%,all samples were subjected to 4 freeze-thaw cycles for a long time,and the RSD was less than 6%.The methodological investigation met the requirements.A total of 35 pediatrics were included in this study?PNA 68.74±177.86 weeks?.A total of 71 serum trough concentrations of vancomycin were determined.The serum trough concentrations were measured 2.03 times per capita.The mean trough concentrations of all pediatrics were 14.72±8.54?g·ml-1 for the first time.The rate of reaching the standard concentration for the first time was 62.86%.Among the pediatrics reaching the standard concentration for the first time,the effective rate of clinical treatment was 77.27%.Acute kidney injury?AKI?occurred only in 2 of the 35pediatrics.A total of 13 cases of liver injury were observed in this study:7 cases of children with liver injury occurred when the concentration of vancomycin was determined for the first time,and the remaining 6 cases occurred when the concentration of vancomycin was not measured for the first time.All pediatrics with liver injury recovered after administration adjustment of vancomycin and hepatoprotective treatment.No hearing impairment was observed in this study. 16 pediatrics were used to validate the prediction accuracy and fitness of the vancomycin PPK model and the trough concentration prediction model constructed by JPKD software.The prediction performance of the model was good with MAE=1.76,RMSE=1.66,MAE<2.5 mg·L-1 and RMSE<4 mg·L-1.Deming regression equation is:y=-1.6402+1.0815 x,95%confidence region of overall intercept a is?-5.9168,2.6363?;95%confidence interval of overall regression coefficient b is?0.7938,1.3692?,and the model fits well.Conclusions:The HPLC method established in this study for the determination of vancomycin serum trough concentration in pediatric patients is accurate and reliable,and is suitable for the application in our hospital.Our hospital uses 10-20?g·ml-1 as the target range.In this range,the effectiveness of anti-infective treatment for pediatrics is high and no obvious adverse reactions occur.This concentration range is reasonable as the target concentration range.Under the dosing regimen recommended in the instruction and clinical guidelines,the compliance rate of serum vancomycin concentration inpediatrics is low and the trough concentration varies greatly individually,so,it is recommended to monitor vancomycin serum concentration combing with JPKD software with Bayesian feedback method to predict vancomycin serum concentration or accurate administration dose.When vancomycin is used in pediatric patients,liver injury is more common than kidney injury.Besides the routine monitoring of renal function,liver function should be routinely monitored.The new model of vancomycin TDM and individualized drug administration in our hospital designed by this study is feasible and effective.It is suitable for the pediatric vancomycin pharmaceutical care service.This new work mode is an important means for clinical pharmacists to participate in anti-infective pharmaceutical services in our hospital,which fully reflects the professional value of clinical pharmacists in pediatric anti-infective pharmaceutical services. |
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