Helicobacter pylori be eradicated with high - dose proton pump inhibitor in extensive metabolizers with the CYP 2 C 19 genotypic polymorphism ?

The CYP2C19 genotypic polymorphism significantly affects the success of Helicobacter pylori (HP) eradication treatment1. All current treatment options for the eradication of H. pylori infection involve the combination of a proton pump inhibitor (PPI) and antibiotics2. PPIs are indispensable in the eradication of H. pylori infection, and the rationale for their use involves a number of potential mechanisms. PPI components with antisecretory properties increase gastric pH, therefore stabilizing acid-labile antibiotics in the stomach, and increase gastric luminal antibiotic concentrations3-5. PPI metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver, mainly S-mephenytoin-4-hydroxylase, which is encoded by CYP2C196-7. 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. HP cannot be eradicated in HomEM due to the insufficient rise in intragastric pH and the low level of antibiotic bioavailability8. 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. 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.