Effects of genotypic differences in CYP2C19 status on cure rates for Helicobacter pylori infection by dual therapy with rabeprazole plus amoxicillin

Citation
T. Furuta et al., Effects of genotypic differences in CYP2C19 status on cure rates for Helicobacter pylori infection by dual therapy with rabeprazole plus amoxicillin, PHARMACOGEN, 11(4), 2001, pp. 341-348
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOGENETICS
ISSN journal
0960-314X → ACNP
Volume
11
Issue
4
Year of publication
2001
Pages
341 - 348
Database
ISI
SICI code
0960-314X(200106)11:4<341:EOGDIC>2.0.ZU;2-V
Abstract
Rabeprazole is a potent proton pump inhibitor and is mainly reduced to thio ether rabeprazole by a non-enzymatic pathway and partially metabolized to d emethylated rabeprazole by CYP2C19 in the liver, We intended to determine a cure rate for Helicobacter pylori infection by dual rabeprazole/amoxicilli n therapy in relation to CYP2C19 genotype status prospectively. Ninety-seve n patients with gastritis and H. pylori infection completed the dual therap y with 10 mg of rabeprazole bid and 500 mg of amoxicillin tid for 2 weeks, At 1 month after treatment, cure of H. pylori infection was assessed on the basis of histology, a rapid urease test, culture, polymerase chain reactio n (PCR), and C-13-urea breath test, CYP2C19 genotype status was determined by a PCR-restriction fragment length polymorphism method, Of the 97 patient s, 33 were homozygous extensive metabolizers (homEM), 48 were heterozygous extensive metabolizers (hetEM), and 16 were poor metabolizers (PM). Cure of H. pylori infection was achieved in 79 of the 97 patients (81.4%, 95%CI= 7 1.9-88.7), Significant differences in cure rates among the homEM, hetEM, an d PM groups were observed; 60.6% (95%CI= 42.1-77.3), 91.7% (95%CI=80.0-97.7 ), and 93.8% (95%CI= 69.8-99,8), respectively (P = 0.0007), Twelve patients without cure after initial treatment (10 homEMs and 2 hetEMs) were success fully retreated with rabeprazole 10 mg q.i.d. and amoxicillin 500mg q,i,d, for 2 weeks. The cure rates for H. pylori infection by dual rabeprazole/amo xicillin therapy depended on the CYP2C19 genotype status, This dual therapy appears to be effective for hetEM and PM patients, However, high dose dual rabeprazole/amoxicillin therapy was effective even for homEM patients, The refore, the genotyping test of CYP2C19 appears to be a clinically useful to ol for the optimal dual treatment with rabeprazole plus amoxicillin. Pharma cogenetics 11:341-348 (C) 2001 Lippincott Williams & Wilkins.