Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin

Citation
T. Furuta et al., Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin, CLIN PHARM, 69(3), 2001, pp. 158-168
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
69
Issue
3
Year of publication
2001
Pages
158 - 168
Database
ISI
SICI code
0009-9236(200103)69:3<158:EOGDIC>2.0.ZU;2-R
Abstract
Background: Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver. The therapeutic effects of prot on pump inhibitors are assumed to depend on CYP2C19 genotype status. Objective: We investigated whether CYP2C19 genotype status was related to e radication rates of H pylori by triple proton pump inhibitor-clarithromycin -amoxicillin (INN, amoxicilline) therapy and attempted to establish a strat egy for treatment after failure to eradicate H pylori. Methods: A total of 261 patients infected with H pylori completed initial t reatment with 20 mg of omeprazole or 30 mg of lansoprazole twice a day, 200 mg of clarithromycin three times a day, and 500 mg of amoxicillin three ti mes a day for 1 week. CYP2C19 genotypes of patients were determined with po lymerase chain reaction-restriction fragment length polymorphism analysis. Patients without eradication after initial treatment were retreated with 30 mg of lansoprazole four times daily and 500 mg of amoxicillin four times d aily for 2 weeks. Results: Eradication rates for Hpylori were 72.7% (95% confidence interval, 64.4%-81.8%), 92.1% (confidence interval, 86.4%-97.3%), and 97.8% (confide nce interval, 88.5%-99.9%) in the homozygous extensive, heterozygous extens ive, and poor metabolizer groups, respectively. Thirty-four of 35 patients without eradication had an extensive metabolizer genotype of CYP2C19. Ninet een of those patients were infected with clarithromycin-resistant strains o f Hpylori. However, there were no amoxicillin-resistant strains of Hpylori. Re-treatment of H pylori infection with dual high-dose lansoprazole-amoxic illin therapy succeeded in 30 of 31 patients with extensive metabolizer gen otype of CYP2C19. Conclusion: The majority of patients without initial eradication of Hpylori had an extensive metabolizer CYP2C19 genotype but were successfully re-tre ated with high doses of lansoprazole and an antibiotic to which Hpylori was sensitive, such as amoxicillin, even when the patients were infected with clarithromycin-resistant strains of Hpylori.