The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

Abstract

Background/Aims: The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole-and rabeprazole-based triple therapies. Methods: A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C 13 -urea breath test. Results: Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795). Conclusions: The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.

Comparison of 10‐day levofloxacin bismuth‐based quadruple therapy and levofloxacin‐based triple therapy for Helicobacter pylori

“…CYP2C19 genotypes may influence the metabolism of various PPIs, and the use of high‐dose or low‐dose PPI may be related to the efficacy of bismuth‐containing therapies . We chose rabeprazole 20 mg twice daily, because rabeprazole is not affected by CYP2C19 genetics . We also analyzed the effect of CYP2C19 polymorphism, and found that 23 patients had the Hom‐EM CYP2C19 genotype, but without obvious statistical significance (Table ).…”

“…We also analyzed the effect of CYP2C19 polymorphism, and found that 23 patients had the Hom‐EM CYP2C19 genotype, but without obvious statistical significance (Table ). The choice of PPI may diminish the impact of CYP2C19 genotypes . Interaction between PPIs and clopidogrel has recently been a hot issue.…”

Antiplatelet drug interactions with proton pump inhibitors

“…In addition to the non-enzymatic pathway, a small amount of rabeprazole is converted into desmethyl rabeprazole and rabeprazole sulfone by CYP2C19 and CYP3A4, respectively [43,49,62]. Consequently, a number of studies have reported similar values for drug exposure, efficacy and clearance in both healthy volunteers and patients regardless of CYP2C19 genotype status [47,51,55,64,65]. …”

<i>Helicobacter pylori</i> Therapy in Children: A Focus on Proton Pump Inhibitors

“…To our knowledge [55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71], the effect of CYP2C19 polymorphisms on H. pylori eradication rate has not been evaluated in children. In randomized, double-blind, placebo-controlled studies of PPI-based triple eradication therapies for H. pylori in children the range of eradication rates has varied between 68 and 74% according to intention-to-treat analysis, and between 69 and 80% per protocol [4].…”

“…Because of the ease of testing, this test may become incorporated in routine practice [54]. However, studies in adults have presented evidence for or against the influence of PPI-related CYP2C19 polymorphisms on eradication rates [55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71]. The systematic review by Klotz et al [72] suggested that HetEM and PM are associated with a significantly higher H. pylori eradication rate in omeprazole and lansoprazole users combined versus HomEMs.…”