PPIs meet the liver.

Abstract This prospective trial evaluated whether CYP2C19 genotype status was related to eradication rates of Helicobacter pylori using triple therapy with a proton pump inhibitor, clarithromycin, and amoxicillin with an attempt to establish a strategy for treating patients whose H. pylori was not eradicated. Study patients consisted of men and women with endoscopically proven gastric ulcers or duodenal ulcers or long-standing gastritis who were positive for H. pylori using a rapid urease test, culture, and histology. The drug regimen for eradication of H. pylori included 20 mg of omeprazole or 30 mg of lansoprazole b.i.d. (randomly selected for proton pump inhibitor use), 200 mg of clarithromycin t.i.d. , and 500 mg of amoxicillin t.i.d. for 1 wk. Patients with gastric or duodenal ulcer were treated with a daily dose of 20 mg of omeprazole or 30 mg of lansoprazole for 5–7 wk after triple therapy. Patients whose H. pylori was not eradicated with the initial regimen were retreated with 30 mg of lansoprazole q.i.d. and amoxicillin q.i.d. for 2 wk. Patients received endoscopic evaluation and confirmation of H. pylori status before treatment and 1 month after the end of all treatments. Endoscopic biopsy samples were obtained for rapid urease testing, bacteriological culture for antimicrobial sensitivity, and polymerase chain reaction analysis for genotyping of CYP2C19 status of patients. Patients were categorized into three groups based upon CYP2C19 genotype: homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers. There were no significant differences between the groups in demographic or disease state measures. Overall, 226 of 261 patients (86.6%) achieved cure of H. pylori infection. Thirty-three of 261 patients were infected with clarithromycin-resistant strains, whereas culture results revealed no amoxicillin-resistant strains. Differences in the status of CYP2C19 genotype and clarithromycin-resistant H. pylori were significantly associated with success or failure of H. pylori eradication. Eradication rates were 72.7% for homozygous extensive metabolizers, 92.1% for heterozygous metabolizers, and 97.8% for poor metabolizers. Thirty-four of 35 patients who did not achieve H. pylori eradication were classified as extensive metabolizers. Thirty-two of these patients were retreated, achieving H. pylori eradication.