Helicobacter pylori Infection and PPI

H. pylori is a major cause of gastritis, peptic ulcer disease, and gastric carcinoma. Eradication of H. pylori with a triple therapy involving a combination of antibiotics (amoxicillin, clarithromycin, metronidazole) and a proton pump inhibitor (PPI) (omeprazole, lansoprazole, rabeprazole) is effective in the treatment of these diseases. Suppression of acid secretion by PPIs increases the concentration of antibiotics and allows H. pylori to reach the growth phase and thus become more sensitive to antibiotics, and PPIs alone have an anti-H. pylori effect (144).

Omeprazole, lansoprazole, and to a lesser extent rabeprazole, are metabolized by CYP2C19 (143). The CYP2C19 PM phenotype comprises 2% to 5% of the Caucasians and 3% to 23% of the Asians, resulting from a single base pair mutation (A to G) in exon 5 of the coding region 7. The truncated mutant protein lacks the heme-binding region and is enzymatically inactive.

Some studies have shown that the therapeutic effects of PPIs and therefore the cure rates for H. pylori infection are significantly dependent on the CYP2C19 genotype status [PM, heterozygous extensive metabolizers (hetEM), and homozygous extensive metabo-lizers (homEM)]. A better cure rate was achieved with dual therapy rabeprazole and amoxicillin in patients with the PM genotype (93.8%) than the hetEM (91.7%) or the homEM (60.6%) genotype (145). In a second study using triple therapy including a PPI and amoxicillin and clarithromycin, the majority of patients without initial eradication of H. pylori were all EM of CYP2C19 (146). Some studies have failed to document an influence of CYP2C19 genetic polymorphism on the efficacy of PPI with amoxicillin and clarithromycin in eradicating H. pylori (147-149). These conflicting reports can be partially explained by the differences in patient inclusion criteria (some included only patients with gastric ulcer disease) (148), patient characteristics (one study included disproportionate number of smokers) (147), and dosage differences in the PPI (150). The inclusion of clarithromy-cin in the triple therapy regimen can also influence the response, because clarithromycin can interact with the other drugs, leading to an altered response. Despite these conflicting reports, some authors have suggested that genotyping for CYP2C19 prior to treatment with a PPI might be a clinically useful and cost-effective tool for optimal treatment of H. pylori infection (151).

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