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
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.