A Meta-analysis Of The Effect Of CYP2C19 Gene Polymorphism On The Metabolism Of Pantoprazole And The Efficacy Of Pantoprazole-based HP Eradication Regimens

Objective:To systematically evaluate the influence of CYP2C19 gene polymorphism on the pharmacokinetics of pantoprazole and the efficacy of eradication of Helicobacter pylori(HP),and to provide evidence-based reference for its clinical individualized medication.Methods:The domestic and foreign studies about the influence of CYP2C19 gene polymorphisms on the pharmacokinetics of pantoprazole and the efficacy of eradication of HP were retrieved from PubMed,Embase,Web of Science,CBM,CNKI,WanFang Data and VIP database.The retrieval time was from their establishment to November,2020.Then to screen and evaluate the quality of the included literatures,extract the datas,and use Revman5.3 for quantitative Meta-analysis.Results:A total of 222 healthy subjects were included in 9 studies in pharmacokinetic section.Meta-analysis results showed that for AUC0-∞ and Cmax,poor metabolizers(PM)were significantly increased compared with other metabolic phenotypes(P<0.00001,P<0.0001).For t1/2,PM were significantly longer than other metabolic phenotypes(P<0.00001).For CL/F,PM were significantly lower than other metabolic phenotypes(P<0.00001).Totally 9 studies were included in pharmacodynamics section,involving 1009 subjects,the results of Meta-analysis showed that:the PM had a better eradication of HP than the homozygous extensive metabolisers(homEM)and the difference was statistically significant(P=0.003),the PM had a slightly better eradication of HP than the heterozygous extensive metabolisers(hetEM)but the difference was not statistically significant(P=0.11),and there was no statistical difference between the homEM and hetEM(P=0.15).Conclusion:CYP2C19 gene polymorphism had a certain influence on the pharmacokinetics of pantoprazole,and its bioavailability was the highest and metabolic clearance was the slowest in the PM group.Clinical efficacy may be different due to the different bioavailability and clearance time of each metabolome.Meta-analysis of the effect of CYP2C19 gene polymorphism on pantoprazole eradication of HP showed that it had an impact on pantoprazole eradication of HP.The PM group had a better eradication effect than the extensive metabolisers(EM)group,especially homEM,while there was no significant difference between homEM and hetEM.Therefore,before the clinical use of pantoprazole in the treatment of HP infection and acid-related diseases,it is recommended to conduct genotype detection to reduce adverse drug reactions,so as to achieve the purpose of individualized treatment.