Pharmacogenetic management concerning efficacy and safety of proton-pump inhibitors

Pharmacogenetic management concerning efficacy and safety of proton-pump inhibitors

E.N. Kareva^1,2

¹I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow

²Pirogov Russian National Research Medical University, Moscow

Proton-pump inhibitors (PPIs) are used to treat acid-related diseases. Despite the recognized PPIs efficacy and safety, some patients do not have an adequate response or develop adverse events related to treatment. The variability of patients’ response to medicinal products may be associated with different mechanisms, but commonly this is due to the variability of metabolic enzymes genotype (rapid and poor metabolizers), which affects the effective drug concentration in the blood. One of the main PPI metabolism enzymes is CYP2C19. Large epidemiological studies confirm the association between the PPIs concentration and CYP2C19 gene polymorphism, resulting in variations of efficacy and safety. The article presents data on the pharmacokinetics and pharmacodynamics of currently available PPIs with an assessment of cytochrome isoforms in their metabolism and the potential role of CYP2C19 genetic variation in the therapeutic PPIs efficacy. The article also shows current recommendations for dosage modification of omeprazole, lansoprazole, pantoprazole, and dexlansoprazole depending on the patient’s metabolic phenotype. There is no need in rabeprazole dosage modification due to the peculiarities of its metabolism. Genotype-based dosage promises to improve therapeutic outcomes and minimize adverse events.

Keywords: gene polymorphism, personalized medicine, omeprazole, lansoprazole, pantoprazole, rabeprazole, metabolizers, CYP2C19.

For citation: Kareva E.N. Pharmacogenetic management concerning efficacy and safety of proton-pump inhibitors. RMJ. 2021;4:68–73.