| Objective: Based on the differences in population pharmacokinetic performance of valproic acid among epileptic patients in xinjiang,such as gender,age,weight,combined drug use and other factors,The population pharmacokinetic model of valeric acid and related literatures and data on the effect of CYP2C19 gene polymorphism on the plasma concentration of valproic acid,using the systematic review meta analysis method,comprehensively elaborate the CYP2C19 gene polymorphism on valproic acid The effect of blood concentration.Methods:(1)Blood drug concentration monitoring data and clinical data were collected from 188 epileptic patients in the first affiliated hospital of medical college of shihezi university in xinjiang province after taking VPA.The NONMEM software was used to establish a population pharmacokinetic model.A total of 324 cases of VPA blood concentration data were investigated.The covariates(sex,age,body weight,combined medication,and ethnicity)were used to investigate the clearance rate(CL)and apparent volume of distribution(V),Through the internal verification method GOF,to examine the predictive effectiveness of the model,to verify and evaluate the final model.(2)Computer search China Knowledge Network(CNKI),China Biomedical Literature Database(CBM),Weipu Chinese scientific journal database,Wanfang Data Knowledge Service Platform,Embase,PubMed database,Cochrane Library database,the search period is from the construction of the database to December 31,2018,Metadata analysis of the experimental data on the effect of CYP2C19 gene polymorphism published at home and abroad on VPA blood concentration using RevMan5.3 software.Results:(1)The final model of population pharmacokinetics was CL=0.138*((WT/70)**0.203*((TDD/70)**0.549)*(1.05**CBZ)*(1.24**LTG)*EXP(ETA(1)),V=25.4* EXP(ETA(2)).By using the internal verification GOF method,parameter estimates and standards are obtained.The error,the percentage of relative standard deviation,and the 95% confidence interval finally show that it is roughly consistent with the final model,indicating that the model is stable;body weight,total daily dose,combined carbamazepine and lamotrigine can be introduced into the final model,the remaining covariates cannot be introduced into the final model.(2)According to inclusion criteria and exclusion criteria,5 studies were included in this meta-analysis,with a total of 654 patients.The results of Meta analysis showed that the VPA blood concentration of patients with CYP2C19 *2/*2,*2/*3,*3/*3 genotypes was higher than that of patients with CYP2C19*1/*2,*1/*3 genotypes [weighted mean difference(WMD)=0.67,95% confidence interval(CI)(0.41~0.92).VPA plasma concentrations of patients with CYP2C19*1/*1 genotype[WMD=0.92,95%CI(0.67~1.16),P<0.00001] and patients with CYP2C19*1/*2,*1/*3 genotype and *1/*1 genotype showed no significant difference [WMD=0.19,95%CI(0.08~0.30),P=0.0006].Conclusion:(1)The population pharmacokinetic model established in this study is consistent with the basic model,and the internal evaluation verification model is relatively stable,but it needs toexpand the sample size to apply to clinical practice.At the same time,it is necessary to further investigate the pathophysiology of patients,etc.The pharmacokinetic factors of the acid ultimately achieve individualized administration in patients with epilepsy.(2)According to the result of meta-analysis,CYP2C19 gene polymorphisms and the blood drug concentration of VPA/body quality correlation,through the analysis of valproic acid in patients with blood drug concentration and drug adverse reactions and curative effect of patients,can consider to patients to test the CYP2C19 gene,help clinical choose appropriate VPA dose to control their blood drug concentration range.Since the number of included studies is small and the sample size is small,a large number of samples and high-quality studies are needed to confirm this conclusion. |
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