p450 - publications
The prevalence of CYP2C19 mutations in Turkish patients with dyspepsia and influence on H. pylori eradication therapy.
Turk J Gastroenterol. 2012 Dec;23(6):805-6
Authors: Celebi A
We read with great interest the paper by Ozdil etal. published in your journal entitled "Influence of CYP2C19 functional polymorphism on Helicobacter pylori eradication" (1). In that paper, they reported that cytochrome P450 2C19 (CYP2C19) polymorphism has an impact on H. pylorieradication, and heterozygous CYP2C19 extensive metabolizers (hetero EMs) had statistically significantly better H. pylorieradication rates compared with homozygous extensive metabolizers (homo EMs). CYP2C19 is an enzyme that functions in the metabolism of drugs such as clopidogrel, barbiturates and diazepam, as well as proton pump inhibitors (PPIs). Among these drugs, while PPIs, barbiturates and anxiolytics are metabolized to inactive metabolites, clopidogrel is metabolized to its active form by the same enzyme system. CYP2C19 genotypes are classified into three groups as rapid metabolizers with wild type genes on both alleles (homo EMs), intermediate metabolizers with a mutation on one allele (hetero EMs) and poor metabolizers with tations on both alleles (PMs). Taking into account our study and other studies from our country on the CYP2C19 polymorphism, it is seen that 75-84% of our population are homo EMs. In these studies, the rate of PMs is 1-5%. While these results are close to the results of the Caucasian race, they are quite different from Asian results, in which the rate of PMs is about 20% (2). Intragastric pH generated by PPIs is higher in PMs compared with homo or hetero EMs. As it is known that high intragastric pH enhances the efficacy of antibiotics, high intragastric pH is important in the eradication therapy (3). One metaanalysis showed that CYP2C19 polymorphism affects eradication rates only in omeprazole-based therapies and has no significant effect in lansoprazole- and rabeprazole-based therapies (4). In another meta-analysis, it was shown that CYP2C19 polymorphism affects mostly omeprazole, followed by pantoprazole and lansoprazole, while rabeprazole is the least affected. Another important finding of this study is at twice-daily double dose of PPI results in a 0.5 point higher pH compared with twice-daily single dose of PPIs (5). It is thought that rabeprazole is less affected by the CYP2C19 polymorphism as it also has non-enzymatic metabolization. Therefore, rabeprazole-based triple therapies may provide an advantage in H. pylorieradication therapy of EMs. In addition, besides dose increments of PPI in homo EMs, the second important feature that should be taken into consideration is that it takes about five days for PPIs to reach the fixed effect level. Our study, in which we evaluated the effects of four different PPIs (esomeprazole, lansoprazole, pantoprazole and rabeprazole) on intragastric pH levels, showed that mean intragastric pH levels and pH < 4 time percentage achieved by the drugs were 10-20% higher on the fifth day compared with the first day (unpublished data). When these results are considered, it seems logical to investigate the efficacy of H. pylorieradication protocols using double-dose PPIs instead standard dose and starting PPIs at least five days prior to antibiotics in our population, in which 80% are homo EMs, and also to investigate whether these protocols increase the eradication rates.
PMID: 23864462 [PubMed - in process]