CYP2C19 polymorphism and proton pump inhibitor response: Implications for genotype-guided dose individualisation

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Background: Proton pump inhibitor (PPI) efficacy varies widely among individuals, and CYP2C19 genetic polymorphism is a key determinant of this variability. Yet pharmacogenomic data from Latin American populations remain limited, and few centres have tested whether genotype-guided dose adjustment improves clinical outcomes in routine practice. Objective: This research aimed to characterise CYP2C19 polymorphism frequencies in a Chilean patient cohort, evaluate the pharmacokinetic and pharmacodynamic consequences of metaboliser status on omeprazole response, and determine whether genotype-guided dose escalation improves Helicobacter pylori eradication rates. Materials and Methods: A prospective pharmacogenomic cohort research enrolled 186 adults requiring PPI therapy at the Valparaiso Academy of Clinical Pharmacology, Chile, between March 2022 and August 2023. Participants were genotyped for CYP2C19*2, *3, and *17 alleles by real-time PCR. All underwent 24-hour intragastric pH monitoring after a single 20 mg omeprazole dose. In Phase A, all participants received standard 20 mg dosing for H. pylori eradication. In Phase B, extensive metaboliser (EM) and ultrarapid metaboliser (UM) participants received an escalated 40 mg dose. Results: Metaboliser distribution was UM 8.6%, EM 43.0%, intermediate metaboliser (IM) 34.4%, and poor metaboliser (PM) 14.0%. Chilean allele frequencies were *1 68.5%, *2 12.8%, *3 0.9%, and *17 17.8%. Mean 24-hour pH ranged from 2.9 (UM) to 6.1 (PM), and the proportion of time above pH 4.0 ranged from 38.2% (UM) to 82.7% (PM). Omeprazole AUC differed 5.6-fold between PM and UM groups. Standard-dose eradication rates were 96.2% (PM), 88.5% (IM), 72.4% (EM), and 58.1% (UM). Genotype-guided dosing raised EM eradication to 89.7% (p < 0.01) and UM eradication to 84.3% (p < 0.001). Conclusion: CYP2C19 metaboliser status predicts PPI pharmacokinetics and H. pylori eradication success. Genotype-guided dose escalation brings EM and UM eradication rates above the 80% benchmark, supporting pharmacogenomic testing in PPI-based treatment protocols.