Effect of CYP2C19 Gene Polymorphisms on Proton Pump Inhibitor, Amoxicillin, and Levofloxacin Triple Therapy for Eradication of Helicobacter Pylori

Background The effects of PPI are variable owing to the CYP2C19 polymorphisms. However, whether the polymorphisms could affect the Hp eradication efficacy of triple therapy is still not clear. The present study aimed to assess the effects of CYP2C19 gene polymorphisms on proton pump inhibitor (PPI), amoxicillin, and levofloxacin triple therapy for Helicobacter pylori (Hp) eradication. Material/Methods We randomly assigned 160 Hp-positive patients with chronic gastritis to 2 groups to receive either 20 mg bid omeprazole (OAL group, n=80) or 10 mg bid rabeprazole (RAL group, n=80), combined with 1000 mg bid amoxicillin and 500 mg qd levofloxacin. The 2 groups were treated for 10 days. The CYP2C19 genotypes included wild-type, M1 mutant gene (*2, the mutation of exon 5), and M2 mutant gene (*3, the mutation of exon 4) identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFIP). According to CYP2C19 genotype combinations, the patients were divided into extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) subgroups. The eradication efficacy of Hp was evaluated by 14C-UBT at 28 days after treatment. Results The trial was completed by 155 patients. Hp eradication rates in OAL and RAL groups were 78.2% and 88.3%, respectively, on per-protocol (PP) analysis, indicating no significant difference (P>0.05). Regarding CYP2C19 genotypes, eradication rates of 60.7%, 84.2%, and 100% were obtained for EM, IM, and PM subgroups, respectively, of the OAL group. EM group eradication rates were significantly lower than IM and PM group values (P<0.05). In the RAL group, no such difference was observed (P>0.05). Hp eradication rates were significantly lower in the EM subgroup of the OAL group compared with that of the RAL group. Conclusions Hp eradication rates were higher in the RAL group than in OAL-treated patients. Interestingly, omeprazole-based therapy was significantly affected by the CYP2C19 genotype, unlike the rabeprazole-based therapy.

[1]  R. Vilaichone,et al.  Effects of the CYP2C19 genetic polymorphism on gastritis, peptic ulcer disease, peptic ulcer bleeding and gastric cancer. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[2]  D. Ochoa,et al.  Evaluation of the relationship between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, pantoprazole and rabeprazole. , 2014, Pharmacogenomics.

[3]  D. Forman,et al.  The fight against gastric cancer - the IARC Working Group report. , 2014, Best practice & research. Clinical gastroenterology.

[4]  Deng-Chyang Wu,et al.  CYP2C19 polymorphism influences Helicobacter pylori eradication. , 2014, World journal of gastroenterology.

[5]  H. Blume,et al.  Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update , 2014, Drug Safety.

[6]  E. Savarino,et al.  The pharmacokinetics of ilaprazole for gastro-esophageal reflux treatment , 2013, Expert opinion on drug metabolism & toxicology.

[7]  Y. Akamine,et al.  The (R)-omeprazole hydroxylation index reflects CYP2C19 activity in healthy Japanese volunteers , 2013, European Journal of Clinical Pharmacology.

[8]  Candong Li,et al.  In Vitro Assessment of Cytochrome P450 2C19 Potential of Naoxintong , 2012, Evidence-based complementary and alternative medicine : eCAM.

[9]  S. Moss,et al.  Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma. , 2011, Cancer letters.

[10]  Zhaoshen Li,et al.  [Levofloxacin-based triple therapy for first-line Helicobacter pylori eradication treatment: a multi-central, randomized, controlled clinical study]. , 2010, Zhonghua yi xue za zhi.

[11]  Jyh-Chin Yang,et al.  CYP2C19 genotypes in the pharmacokinetics/pharmacodynamics of proton pump inhibitor-based therapy of Helicobacter pylori infection , 2010, Expert opinion on drug metabolism & toxicology.

[12]  H. Sugimura,et al.  Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection , 2005, Alimentary pharmacology & therapeutics.

[13]  Hong Wang,et al.  [The effect of proton pump inhibitor on intragastric acidity and it relation to S-mephenytoin hydroxylase genetic polymorphism]. , 2003, Zhonghua nei ke za zhi.

[14]  A. Peregrina,et al.  CYP2C19‐ and CYP3A4‐Dependent Omeprazole Metabolism in West Mexicans , 2003, Journal of clinical pharmacology.

[15]  J. Gisbert,et al.  Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta‐analysis , 2002, Alimentary pharmacology & therapeutics.

[16]  P. Zaphiropoulos,et al.  The human CYP2C locus: a prototype for intergenic and exon repetition splicing events. , 2000, Genomics.

[17]  J. Goldstein,et al.  Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. , 1997, The Journal of pharmacology and experimental therapeutics.

[18]  U. Meyer.  Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs , 1996, European journal of gastroenterology & hepatology.

[19]  G R Wilkinson,et al.  The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. , 1994, The Journal of biological chemistry.

[20]  R. Shi,et al.  Levofloxacin containing triple therapy vs standard triple therapy for eradication of Helicobacter pylori: A Meta-analysis , 2014 .

[21]  Chun-Chao Chang,et al.  Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism , 2008, European Journal of Clinical Pharmacology.

[22]  L. Xu.  Prevalence of Helicobacter pylori Resistance to Antibiotics and its Influence on the Treatment Outcome in China:A Multicenter Clinical Study , 2007 .