Population Pharmacokinetics Of Vancomycin In Elderly Patients In Jiamusi Area

Objective To establish the HPLC method for the determination of vancomycin blood concentration in human plasma,and to compared the consistency relationship between HPLC method and the existing FIPA method.The JPKD software was used to simulate the old people pharmacokinetic model of vancomycin after intravenous injection in this region,and the application was validated by this model to guide the practical application.Methods A method for determining the concentration of vancomycin in plasma by HPLC using metronidazole as an internal standard and triethylamine phosphate-methanol as a mobile phase.Seventy-one plasma samples were collected for clinical detection of vancomycin plasma concentration.Plasma concentrations were determined by HPLC and FPIA,respectively.Paired sample t-test and Bland-Altman and regression analysis were used to compare the consistency of the two test results.The JPKD model was used to establish a population pharmacokinetic model of vancomycin in the Jiamusi area,and the model formula was calculated.A total of 138 patients were enrolled in the collection,of which 97 were used for modeling,41 were used for validation,and WRES and linear regression analysis were used to compare the consistency between modeling data and validation data.The NONMEM method was used to establish a vancomycin population pharmacokinetic model,and the consistency between the JPKD method and the NONMEM method was compared.Results The HPLC method established in this experiment determined the vancomycin blood concentration was good,the internal standard,plasma impurities,vancomycin peak separation was complete,and the linear concentration of the test results was good,Y=0.00814X+0.07146,R2=0.9952.The precision,method recovery rate and stability investigation all meet the analysis conditions.The Bland-Altman bias analysis showed that the HPLC method was 1.28?g·mL^-1higher than the FPIA method,p=0.0230,and the 95%difference was within the 95%confidence interval(2.4907-4.0751?g·mL^-1).It is indicated that the above two detection methods are in good agreement.The linear relationship between the results calculated by the formula Cs=Dose×?1-exp?-CL/Vd×Tin??/?Tin×CL×?1-exp?-CL/Vd×Tau???×exp?-CL/Vd×Ts?obtained by the JPKD model and the results obtained by HPLC is good,Y=1.0105X-0.827,R²=0.9618,WRES was?4.88?3.10?,38 cases of WRES<10%.The model made a good prediction of 92.7%vancomycin steady-state trough concentration.The method between the JPKD method and the model fitted by the NONMEM software is in good agreement.Conclusions The formula obtained by fitting the JPKD model was good to predict the dose of vancomycin in the intravenous infusion of vancomycin in patients in Jiamusi area.The model is simple and practical,and it can be used to establish and promote regional pharmacokinetic models more quickly and easily.The monitoring of vancomycin treatment concentration in our hospital helps to promote clinical rational medicine use.