Cytochrome P450 Enzymes in the Metabolism of Proton Pump Inhibitors: Implications for the Treatment of Peptic Ulcers.

Abstract

Introduction: Peptic Ulcer Disease (PUD) remains a prevalent gastrointestinal condition primarily caused by Helicobacter pylori infection and chronic NSAID use. Proton Pump Inhibitors (PPIs) are the mainstay therapy, promoting mucosal healing through profound gastric acid suppression. However, variable clinical outcomes are frequently observed, largely influenced by individual differences in PPI metabolism mediated by cytochrome P450 (CYP450) enzymes, especially CYP2C19 and CYP3A4.

Methods: The review is a critical analysis of the evidence on PPI pharmacokinetics, pharmacogenomics, and drug-drug interactions based on a structured search of PubMed, Scopus, and Web of Science, with predetermined inclusion and exclusion criteria to ensure equal consideration of studies on the topic.

Results: Genetic polymorphisms in CYP2C19 create distinct metabolizer phenotypes-poor, intermediate, extensive, and ultrarapid-that markedly influence PPI plasma levels, intragastric pH control, and ulcer healing rates. Poor metabolizers exhibit superior healing due to prolonged acid suppression, while ultrarapid metabolizers are prone to treatment failure. Rabeprazole and ilaprazole, showing minimal CYP2C19 dependence, provide consistent efficacy across genotypes and reduced drug interaction potential.

Discussion: Pharmacogenomic variability in CYP2C19 significantly affects therapeutic response and adverse outcomes. Personalized therapy based on genotype can optimize PPI efficacy, minimize toxicity, and reduce drug-drug interactions, particularly with agents such as clopidogrel.

Conclusion: Incorporating CYP2C19 genotyping and pharmacogenomic data into clinical decisionmaking may improve treatment individualization, although evidence remains heterogeneous and context-dependent.