Effects of Genetic Polymorphisms of Cytochrome P450 Enzymes and MDR 1 Transporter on Pantoprazole Metabolism and Helicobacter pylori Eradication

Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of peptic ulcer disease ( PUD ) and metabolized by cytochrome P450 ( CYP ) enzymes CYP 2C19 and CYP 3A4. Pantoprazole is a substrate for multi‐drug resistance protein 1 ( MDR 1). Single nucleotide polymorphisms ( SNP s) in CYP 2C19 , CYP 3A4 and MDR 1 affect enzyme activity or gene expression of proteins and may alter plasma pantoprazole concentrations and treatment success in PUD . In this study, we aimed to investigate the association between genetic polymorphisms in CYP 2C19 , CYP 3A4 and MDR 1 and pharmacokinetics of pantoprazole and therapeutic outcome in patients with either Helicobacter pylori ‐associated [H.P.(+)]‐ PUD or [H.P.(+)]‐gastritis. The plasma pantoprazole concentrations were determined by using an HPLC method at the third hour after a 40‐mg tablet of pantoprazole administration in 194 newly diagnosed patients with either [H.P.(+)]‐ PUD or [H.P.(+)]‐gastritis. Genotyping was performed by using PCR ‐ RFLP and DNA sequencing. Among patients appearing for follow‐up examination (n = 105), the eradication rate for H. pylori was 82.8% (n = 87). The median pantoprazole plasma concentrations in poor metabolizers ( PM ), rapid metabolizers ( RM ) and ultrarapid metabolizers ( URM ) were 2.07, 1.69 and 1.28 μg/ml, respectively ( p = 0.04). CYP 3A4*1G and *22 polymorphisms did not affect plasma pantoprazole concentrations and H. pylori eradication rate. The MDR 1 genetic polymorphisms did not affect plasma pantoprazole concentrations. MDR 1 3435 CC ‐2677 GG ‐1236 CC haplotype carriers had lower H. pylori eradication rate (60%) than the remaining subjects (84.9%) while the difference was not statistically significant ( p = 0.07). In conclusion, while CYP 2C19 genetic polymorphisms significantly affected plasma pantoprazole concentrations, polymorphisms of CYP 2C19 , CYP 3A4 and MDR 1 did not affect H. pylori eradication rates.