Pharmacokinetics Study And Drug Concentration Monitoring Of Vancomycin In Human Cerebrospinal Fluid

Objective:A high performance liquid chromatographic method was established to detect vancomycin drug concentration in the serum and cerebrospinal fluid.To explore the pharmacokinetic characteristics of vancomycin and its related influencing factors in cerebrospinal fluid of vancomycin in two different administration ways,which are intravenous infusion of vancomycin 1g every 8 hours with or without lumbar cistern drainage tube injection of vancomycin 20mg every 24 hours.Then,monitor the cerebrospinal fluid trough concentration and serum trough concentration.Study the clinical efficacy,safety and related influencing factors under different modes of administration,to provide a reference for patients with central nervous system infection in neurosurgery.Methods:By determining the optimal chromatographic conditions and methods for processing blood and cerebrospinal fluid samples,a method for detecting vancomycin drug concentrations in serum and cerebrospinal fluid by high-performance liquid chromatography was established,and methodological investigations were conducted.Patients who were admitted to our department of neurosurgery from August 2018 to September 2019 and met the requirements for inclusion were collected.Blood and cerebrospinal fluid samples were collected from patients,and vancomycin drug concentrations were measured using high-performance liquid chromatography.For patients who meet the requirements for inclusion in pharmacokinetic studies,take cerebrospinal fluid samples and measure drug concentrations according to the designed sample collection time points,draw drug concentration-time curves,and calculate pharmacokinetic parameters.The data was sorted and analyzed by SPSS 22 software,and plotted using GraphPad Prism 5 drawing software.Results:The linear relationship between vancomycin drug concentration in serum in the range of 5.00¹00.00mg�L^-1 is good,the lower limit of quantification is 5.00mg�L^-1,the regression equation is y=2618.2x+951.89,and R2=0.9966;the linear relationship between vancomycin drug concentration in the cerebrospinal fluid in the range of0.20²000.00mg�L^-1 was good,and the lower limit of quantification was 0.20mg�L^-1.The regression equation was y=6177.9x�124678,and R2=0.9977.The high performance liquid chromatographic methodological examination meets the requirements and has a good specificity.The recovery rate of serum and cerebrospinal fluid samples is in the range of 96.30%to 106.12%,and the RSD is<4%.Both of the intra-day and inter-day RSDs are<7%.After standing at room temperature for 0 hours,12 hours,and 24 hours,and repeatedly freezing and thawing at-80�C for 1,2,and 3times,the RSDs were all less than 7%.A total of 15 patients were included in the study of vancomycin pharmacokinetics in cerebrospinal fluid.A total of 138 cerebrospinal fluid samples were collected according to the sampling time point.The pharmacokinetic parameters of 9 patients with intravenous vancomycin in group A were:AUC_0-8h=40.56�7.51mg�L^-1�h,t_1/2=8.85�5.57h,C_max=7.73�2.33mg�L^-1,C_min=3.63�1.08mg�L^-1.Pharmacokinetic parameters of 6 patients in group B administered with intravenous infusion of vancomycin combined with lumbar cistern drainage tube injection:AUC_0-8h=1847.00�1522.79mg�L^-1�h,t_1/2=3.30�1.55h,C_max=758.36�663.84mg�L^-1,C_min=27.82�12.93mg�L^-1.The differences in AUC_0-8h,t_1/2,C_max,C_min,AUC_0-8h/MIC between patients in group A and group B were statistically significant?P<0.05?.In the study of vancomycin drug concentration in serum and cerebrospinal fluid of neurosurgery patients,38 patients were included in the study,45 serum trough concentration samples were retained,and the serum trough concentration range was6.13 to 77.16 mg�L^-1,with a median of 19.78?17.52,23.45?mg�L^-1.Vancomycin serum trough concentration there was a statistically significant difference in vancomycin administration patterns between each concentration group?P<0.001?.A total of 117samples of cerebrospinal fluid valley concentration were collected from 38 patients.In the a mode of administration?intravenous infusion of vancomycin?,a total of 59cerebrospinal fluid valley concentration samples were retained,with a concentration range of 0.20 to 14.89 mg�L^-1,with a median of 3.95?2.28,5.77?mg�L^-1;In the b mode of administration?intravenous infusion of vancomycin combined with injection in the lumbar cistern drainage tube?,a total of 58 cerebrospinal fluid valley concentration samples were retained,with a concentration range of 6.54 to 339.29 mg�L^-1,with a median of 23.94?14.63,53.27?mg�L^-1.The trough concentration of cerebrospinal fluid in patients with b administration was significantly higher than the trough concentration of cerebrospinal fluid in patients with administration a?P<0.001?.The average medication duration of 38 patients was 9.45�3.80 days.There were no significant differences in clinical effectiveness and days of medication between patients in group C who took the method of administration and patients in group D who took the b method of administration?P>0.05?.Vancomycin serum trough concentration was positively linearly correlated with cerebrospinal fluid trough concentration?P<0.05?;there was a linear relationship between vancomycin serum trough concentration and serum creatinine?R²=0.563,P<0.05?,and there was a positive correlation.During vancomycin administration,two patients developed a drug eruption and one patient had acute kidney injury.There were no local drug-related adverse reactions in patients who received vancomycin injection in the lumbar cistern drainage tube.Conclusion:The HPLC method established in this study to detect vancomycin concentration in serum and cerebrospinal fluid meets the methodological requirements and can meet the detection needs of serum and cerebrospinal fluid samples.Compared with the simple intravenous infusion of vancomycin 1g every 8 hours,the patients with intravenous infusion of vancomycin 1g every 8 hours combined with the injection of vancomycin20mg once every 24 hours in the lumbar cistern drainage tube,which half-life of vancomycin in cerebrospinal fluid is shorter and can significantly increase the area,peak concentration,and valley concentration of the vancomycin drug concentration-time curve in cerebrospinal fluid,and the AUC_0-8h/MIC is greater than 400.Patients with vancomycin intravenous infusion and lumbar large pool injections had higher standard-reaching rates of vancomycin concentration in cerebrospinal fluid and patients have a higher recovery rate,and no related adverse reactions were observed in topical administration,which is suitable for patients with poor curative effect by simple intravenous infusion.During the treatment period,the concentration of vancomycin in the serum and cerebrospinal fluid should be monitored to provide reference for the treatment of patients with central nervous system infection in neurosurgery.