CYP2C19 genotype-guided dosing of proton pump inhibitors: progress in clinical trials and real-world use

ABSTRACT Introduction Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders; however, treatment response varies significantly due to Cytochrome P450 2C19 (CYP2C19) genetic polymorphisms that alter individual drug metabolism. Such variation can lead to insufficient acid suppression, resulting in treatment failure or adverse events. Genotype-guided PPI therapy represents an important step toward personalized gastroenterology by optimizing drug efficacy and safety. Areas covered This review summarizes evidence from clinical trials and meta-analyses examining CYP2C19-mediated differences in the pharmacokinetics and pharmacodynamics of PPIs in both adults and children. Relevant literature was identified primarily through PubMed and clinical guidelines, covering publications from 1989 to 2025. The review focuses on outcomes related to gastroesophageal reflux disease (GERD), Helicobacter pylori eradication, and eosinophilic esophagitis. Current trials indicate that genotype-guided, tailored PPI therapy – through dose adjustment, drug selection, or regimen modification – can improve treatment efficacy and control abdominal symptoms without increasing safety risks or costs. Expert opinion CYP2C19 genotype-guided therapy constitutes a practical approach to personalized medicine for acid-related disorders. Barriers to widespread implementation include limited test availability, uncertain cost-effectiveness, and insufficient clinician awareness. Future directions include integrating multi-gene pharmacogenomic testing, model-informed dosing, and artificial intelligence-based decision support to advance individualized acid suppression and personalized gastroenterology.