Pharmacogenetics of the Proton Pump Inhibitors: A Systematic Review

Abstract

Cytochrome P450 (CYP) 2C19 mediates the major metabolic transformations of the proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole. Genetic polymorphism of CYP2C19 can lead to significant phenotypic variation in the activity of this isoenzyme and thus in the metabolism of PPIs. We systematically reviewed the pharmacogenetic studies of PPIs with respect to the effects of CYP2C19 polymorphism on the clinical outcomes of PPI therapy. We searched MEDLINE (January 1966-August 2002) and EMBASE (January 1988-August 2002) for English-language articles on the pharmacogenetics of PPIs; the search was supplemented by a bibliographic review of all relevant articles. Seventeen pertinent citations were identified, and the quality (level) of evidence for each was categorized according to the rating scale of the United States Preventive Services Task Force. We found that the relationship between CYP2C19 genetic polymorphism and clinical outcomes after PPI therapy has not yet been clearly delineated. Virtually all pharmacogenetic studies of PPIs have been performed in Japanese men; thus, the clinical relevance of CYP2C19 genetic polymorphism in non-Asian patients and women is unknown. Differences among dual- and triple-therapy drug regimens make it difficult to compare H. pylori eradication studies and assess their applicability to current practice patterns. Drug adherence, a pivotal factor in the success of eradication therapy, was addressed in only four trials. Future directions for research include performing more studies with larger sample sizes, particularly in non-Asian populations and women; measuring plasma PPI concentrations to directly correlate H. pylori infection and ulcer cure rates with plasma drug availability; expanding the study population to patients with gastroesophageal reflux disease; and exploring the influence of CYP3A4 in the success or failure of PPI therapy. Although CYP2C19 genotyping is currently only a research instrument, it may be a valuable clinical tool in select patients to ensure optimal PPI therapy.

The prevalence of CYP2C19 mutations in Turkish patients with dyspepsia

“…The distribution of CYP2C19 mutations show variation between the eastern and western parts of the world (2,6). In the present study, we found that only 13 subjects out of 100 dyspeptic patients had heterozygous CYP2C19*2 mutation and 1 patient homozygous CYP2C19*2 mutation.…”

Antibiotic treatment forHelicobacter pylori: Is the end coming?

“…The frequency of CYP2C19 polymorphism differs depending on ethnicity. Asians have a higher proportion of PM compared with Western populations, particularly Caucasians and African-Americans [139,141] . In contrast, Caucasians have a higher prevalence rate of HomEM compared with Asians [142] .…”

Clinical Usefulness of Limited Sampling Strategies for Estimating AUC of Proton Pump Inhibitors

“…31) In addition, recent meta-analysis has reported that PPIs therapy for H. pylori eradication is likely to be eŠec-tive, irrespective of CYP2C19 genotype. 11) Unfortunately, plasma concentrations of PPIs were not measured in those studies.…”