Effects of genetic differences in CYP2C19 status on cure rates of Hericobacter pylori infection by dual rabeprazole/amoxicillin therapy in comparison with dual omeprazole/amoxicillin therapy

Abstract

Backgrounds and Aims: Omeprazole (OPZ) is mainly metabolized by S-mephenytoin 4' -hydroxylase (CYP2CI9) in the liver. On the other hand, rabeprazole (RPZ), a new proton pump inhibitor, is mainly metabolized to thioether-RPZ by non-enzymatic pathway and partially metabolized to demethylated-RPZ by CYP2CI9 in the liver. The therapeutic effect of OPZ is more affected by genetic differences in CYP2C19 status than that of RPZ. This study aimed to determine whether CYP2CI9 genotype status is associated with the eradication rate of Helicobacterpylori (Hp) by a dual RPZlamoxicillin (AMPC) therapy in comparison with a dual OPVAMPC therapy. Methods: 140 patients with Hp positive-peptic ulcer or gastritis were treated with daily doses of 20 mg of RPZ (n=70) or OPZ (n =70) and 1.5-2.0g of AMPC for two weeks. CYP2C19 genotype status for two mutations associated with the poor metabolizer phenotype, CYP2C19ml in exon 5 (ml) and CYP2C19m2 in exon 4 (m2), was determined by a PCR-RFLP method. One month after treatment, eradication rates of Hp were determined on the basis of histology, culture, RUT, 13C-UBT and PCR (J Clin Microbiol1996; 34: 2421-5). Results: Patients were classified into three groups on the basis of CYP2C19 genotyping test results; homEM group (homozygous for the wild-type alleles in both exon 5 and exon 4 [wt/wtj), hetEM group (heterozygous for CYP2C19ml or for CYP2C19m2 [wtlml or wtlm2]), and PM group (heterozygous for the CYP2C19ml and CYP2C19m2 or homozygous for CYP2C19ml [mllm2 or ml/ml]). The eradication rates by a dual RPZlAMPC therapy versus a dual OPVAMPC therapies in different genotype groups were 63.6% (8114) vs 31.0% (9/29) in homEM groups (p=0.0261), 89.5% (34/38)vs 62.1% (18129) in het EM groups (p=0.0160), and 90.0% (9/10) vs 91.6% (11/12) in PM groups (p>0.2). Moreover, the cure rate by the dual RPVAMPC therapy in the hetEM plus PM groups (mutation-positive group) was 89.6% (43/48). Conclusion: The eradication rates by both dual OPZlAMPC therapy and RPZlAMPC were affected by CYP2C19 genotype status. However, the eradcation rate by dual RPZIAMPC therapy was higher than that of dual OPZlAMPC therapy. Moreover, in hetEM and PM patients, the dual RPZIAMPC therapy yielded a sufficiently high eradication rate without second antibiotics, such as clarithromycin or metronidazole. The genotyping test of CYP2C 19 appears to be a useful clinical tool for the optimal selection of PPls. 2662