Introduction
Proton-pump inhibitors (PPIs) are a class of acid-suppressing agents, which are among the most utilized drugs worldwide. They are used to treat gastroesophageal disorders, predominantly gastroesophageal reflux disease (GERD), peptic ulcer disease, Helicobacter pylori infection, erosive esophagitis, Zollinger–Ellison syndrome, and eosinophilic esophagitis (EoE).
The main metabolism pathway of PPIs is cytochrome P450 (CYP450), specifically CYP2C19. There are strong data to support the influence of CYP2C19 genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Patients being treated with a PPI may also benefit from genotype-guided dosing.
Aims & Methods
AIM: To assess the degree of acceptance of pharmacogenetic recommendations for the adjustment of PPIs based on the CYP2C19 phenotype, as well as their impact on clinical outcomes in patients with suboptimal response.
MATERIALS AND METHODS: A retrospective observational study including patients with a lack of response to PPIs in whom CYP2C19 testing was performed between 2024 and 2025. The reason for the request, metabolic phenotype, prescribed PPI and initial dosage were recorded.
Pharmacogenetic recommendations were issued by the Pharmacy Department based on the phenotype. The degree of acceptance (change in treatment) was assessed, and the type of intervention—dose adjustment or change of PPI—as well as treatment following the test, was analysed in a structured manner. The subsequent clinical response was evaluated.
Results
A total of 63 pharmacogenetic tests were included, with the main indication being GERD (74.6%), followed by EoE (19.0%).
The phenotypic distribution was: rapid metabolisers 39.7%, normal 36.5%, intermediate 20.6% and ultra-rapid/poor in smaller proportions.
The most commonly prescribed PPI initially was esomeprazole (54.0%), followed by omeprazole (17.5%) and pantoprazole (12.7%).
Treatment changes were made following pharmacogenetic recommendations in 23 patients (36,5%). Of these, 18 underwent dose adjustment and 8 a change of PPI.
A favourable clinical response was observed in 23 patients (36.5% of the total), mainly following pharmacogenetic intervention.
Conclusion
The use of pharmacogenetics in the management of PPIs in refractory patients enables treatment to be optimised on an individual basis.
Although compliance with the recommendations was moderate, a significant proportion of patients showed clinical improvement following the intervention, which supports its usefulness in clinical practice and the role of the Pharmacy Department in personalised medicine.
References
Rodríguez-Alcolado L, Navarro P, Arias-González L, Grueso-Navarro E, Lucendo AJ, Laserna-Mendieta EJ. Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics. Pharmaceutics. 2024 Apr 2;16(4):487.
Eken E, Estores DS, Cicali EJ, Wiisanen KK, Johnson JA. A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps. Pharmgenomics Pers Med. 2023 Jun 23;16:645-664.
Lima JJ, Thomas CD, Barbarino J, Desta Z, Van Driest SL, El Rouby N, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423