title: Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?
abstract: Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. kadirdmr@yahoo.com.
authors.forename: A
authors.initials: A
authors.lastname: Ormeci
authors.forename: Z
authors.initials: Z
authors.lastname: Emrence
authors.forename: B
authors.initials: B
authors.lastname: Baran
authors.forename: O M
authors.initials: OM
authors.lastname: Soyer
authors.forename: S
authors.initials: S
authors.lastname: Gokturk
authors.forename: S
authors.initials: S
authors.lastname: Evirgen
authors.forename: F
authors.initials: F
authors.lastname: Akyuz
authors.forename: C
authors.initials: C
authors.lastname: Karaca
authors.forename: F
authors.initials: F
authors.lastname: Besisik
authors.forename: S
authors.initials: S
authors.lastname: Kaymakoglu
authors.forename: D
authors.initials: D
authors.lastname: Ustek
authors.forename: K
authors.initials: K
authors.lastname: Demir
mesh_terms: D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*
chemical_list: D054328:Proton Pump Inhibitors; D065731:Cytochrome P-450 CYP2C19