Study On Individualized Clinical Usage Of Vancomycin Based On PK-PD Parameters

Objective:1.Exploring the correlation between vancomycin pharmacokinetics（PK）/pharmacodynamics（PD）parameters and efficacy and safety.Comparing different PK/PD parameters formulated or adjusted therapeutic vancomycin regimens have a distinction in efficacy and safety.2.Optimized high-performance liquid chromatography（HPLC）for determination of vancomycin drug concentration in clinical patients.Establish vancomycin AUC_{0²4 h}calculator and verify.3.Using the AUC_{0²4 h} calculator formulate or adjust therapeutic vancomycin regimens and analyze the correlation between AUC_{0²4 h}/MIC,AUC_{0²4 h} and efficacy and safety.Methods:1.In Chinese and English databases search the literature related to vancomycin therapeutic drug monitoring,screen the original literature,conduct a quality assessment of the included original literature,and extract data related to outcome indicators.Extracted outcome indicators data were analyzed using Review Manager 5.4and STATA 16.0 software.2.HPLC condition for vancomycin was that the column was Agilent ZORBAX SB-C18（250 mm?4.6 mm,5μm）,the mobile phase was acetonitrile-water（containing 25mmol/L potassium dihydrogen phosphate,p H=3.2,V/V=8∶92）,the flow rate was 0.8m L/min,the column temperature was 40℃,and the detection wavelength was 220 nm.After using vancomycin reached to steady state,the clinical monitored the blood concentration of infusion and elimination segments.Based on the one-compartment and first-order kinetic elimination derivation the infusion and elimination calculating formula to establish the AUC_{0²4 h} calculator.3.The solver function in Microsoft Excel was used to calculate individualized K_eand V_d values of patients which bring into the formula to calculate AUC_{0²4 h}/MIC and AUC_{0²4 h}.The evaluation indexes of treatment effect before and after the clinical use of vancomycin were collected,and the correlation between AUC_{0²4 h}/MIC,AUC_{0²4 h}and clinical PD indexes were analyzed by SPSS 25.0.Results:1.Vancomycin trough concentration and AUC correlation with efficacy and safety outcome indicators.There was no statistically significant difference in treatment efficacy between different PK/PD parameters guiding the formulation or adjustment of vancomycin regimens,but regimens formulated or adjusted with AUC resulted in lower AKI incidence and mortality than through concentrations.2.This study established HPLC used to determine vancomycin serum drug concentration.The linear range was 1.18 to 75.8μg/m L,and the standard curve equation was Y=0.0518X-0.0087,R²=0.9998.The accuracy between 92.4%～103.15%.The intra-day and inter-day precision RSD ranged from-7.59%to 3.15%and-11.42%to 0.56%respectively.The recoveries ranged from 91.12%to 99.24%.The HPLC method accordance with the European standard for biological sample detection.Room temperature,4℃,-20℃stability CV within±11%.The established AUC_{0²4 h} calculator has verified the result showed that the calculator performed well predictive.3.Among 32 patients included,there had a significant difference（P<0.05）in decreasing inflammatory indicators before and after medication in the group AUC_0²4h/MIC≥400、AUC_{0²4 h}≥400.There not had a significant difference in inflammatory indicators before and after medication in the group AUC_{0²4 h}/MIC<400、AUC_{0²4 h}<400.In the AUC_{0²4 h}≥600 group,the index of Urea increased before and after drug administration with a statistical difference（P<0.05）.In the AUC_{0²4 h}<600 group,the index of liver and kidney function before and after drug administration was not significant difference.Conclusions:1.Vancomycin trough concentration and AUC were correlated with efficacy and safety.AUC formulated or adjusted vancomycin therapeutic regimens superior to trough concentration in terms of safety.2.The optimized vancomycin blood concentration detection method had strong specificity,high accuracy and sensitivity,and easy operation.The established AUC_{0²4 h}calculator validation results suggest that it performed well predictive and provided a reference for individualized clinical usage of vancomycin.3.Pharmacokinetic parameters AUC_{0²4 h}/MIC≥400 and AUC_{0²4 h}≥400 correlation with clinical efficacy.When AUC_{0²4 h}≥600 we should alert to the development of renal damage.It shows that vancomycin AUC_{0²4 h} is safety and efficacy in the range of400～600 mg·h·L^-1.