Image3_Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis.TIFF
Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy.
Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included.
Results: A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8–80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3–79.6%), 81.2% (1,498/1,844, 95% CI: 79.3–83.0%) and 86.8% (644/742, 95% CI: 83.9–88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06–1.39, P = 0.006) and 1.57 (95% CI: 1.27–1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar.
Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.
History
References
- https://doi.org//10.1111/hel.12574
- https://doi.org//10.1046/j.1523-5378.2001.00037.x
- https://doi.org//10.1097/00008571-199512000-00004
- https://doi.org//10.1111/j.1365-2125.1995.tb04488.x
- https://doi.org//10.1177/1756284820927306
- https://doi.org//10.22034/APJCP.2017.18.4.927
- https://doi.org//10.1016/s1590-8658%2801%2980043-8
- https://doi.org//10.1111/j.1365-2036.2007.03386.x
- https://doi.org//10.1016/S0009-9236%2899%2970075-5
- https://doi.org//10.1038/sj.clpt.6100043
- https://doi.org//10.1097/00008571-200106000-00009
- https://doi.org//10.1067/mcp.2001.113959
- https://doi.org//10.1067/mcp.2001.119721
- https://doi.org//10.1053/gast.1996.v111.pm8690200
- https://doi.org//10.1111/j.1523-5378.2007.00518.x
- https://doi.org//10.1007/BF01963775
- https://doi.org//10.3748/wjg.v13.i28.3836
- https://doi.org//10.2165/00044011-200626070-00002
- https://doi.org//10.1111/jgh.13233
- https://doi.org//10.1046/j.1440-1746.2002.02790.x
- https://doi.org//10.1046/j.1365-2036.1999.00022.x
- https://doi.org//10.1046/j.1365-2036.2003.01659.x
- https://doi.org//10.1111/apt.14130
- https://doi.org//10.1111/apt.13588
- https://doi.org//10.1111/hel.12597
- https://doi.org//10.1046/j.1365-2036.2003.01406.x
- https://doi.org//10.1111/j.1440-1746.2008.05408.x
- https://doi.org//10.1007/s00228-009-0625-8
- https://doi.org//10.1016/S0009-9236%2896%2990214-3
- https://doi.org//10.1111/j.1365-2036.2007.03298.x
- https://doi.org//10.2165/00044011-200525050-00002
- https://doi.org//10.5009/gnl.2010.4.2.201
- https://doi.org//10.1097/MD.0000000000022137
- https://doi.org//10.1136/gutjnl-2015-310142
- https://doi.org//10.1007/s00228-008-0552-0
- https://doi.org//10.1136/gutjnl-2016-312288
- https://doi.org//10.1136/gut.2007.132514
- https://doi.org//10.1097/00042737-200301000-00006
- https://doi.org//10.1046/j.1365-2036.2002.01368.x
- https://doi.org//10.1111/j.1365-2036.2005.02353.x
- https://doi.org//10.1159/000485097
- https://doi.org//10.7314/apjcp.2016.17.4.1903
- https://doi.org//10.1111/hel.12041
- https://doi.org//10.1111/apt.12492
- https://doi.org//10.1136/gut.43.2008.s56
- https://doi.org//10.1111/j.1365-2036.2005.02281.x
- https://doi.org//10.2169/internalmedicine.56.7823
- https://doi.org//10.1097/MCG.0b013e318243201c
- https://doi.org//10.1046/j.1365-2036.2001.01108.x
- https://doi.org//10.1046/j.1365-2036.2002.01229.x
- https://doi.org//10.1016/j.clpt.2004.06.008
- https://doi.org//10.1111/j.1523-5378.2007.00508.x
- https://doi.org//10.1016/j.clpt.2004.10.010
- https://doi.org//10.3390/antibiotics9100645
- https://doi.org//10.1111/apt.12014
- https://doi.org//10.1111/hel.12128
- https://doi.org//10.3389/fphar.2018.01560
- https://doi.org//10.1007/s00005-009-0007-z
- https://doi.org//10.1136/gutjnl-2019-319954
- https://doi.org//10.1111/j.1572-0241.2003.07707.x
- https://doi.org//10.1371/journal.pone.0062162
- https://doi.org//10.1016/j.cgh.2014.10.036
- https://doi.org//10.1016/0009-9236%2895%2990192-2
- https://doi.org//10.1111/j.1365-2710.2009.01140.x