Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

Abstract

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylorinegative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Randomized, Comparative Study of Standard Dose of Rabeprazole versus Omeprazole in Gerd/Heartburn Symptom Relief

“…Compared with omeprazole 20 mg or lansoprazole 30 mg, rabeprazole 10 mg has been shown to exert a faster and more pronounced inhibition of gastric acid secretion in these healthy Japanese volunteers with the homoEM or heteroEM phenotypes [33]. The findings in this study were in contrast to that obtained in the study of Nagahara et al where omeprazole 20mg was found to be more effective than Rabeprazole 10mg at achieving early, sufficient, sustained reflux symptom relief in individuals with the CYP2C19 PM phenotype, and is similarly effective to rabeprazole 10 mg in those with heteroEM or homoEM phenotypes [36].…”

Effect of Timing of Proton Pump Inhibitor Administration on Acid Suppression

“…The absence of H. pylori infection was confirmed by measuring H. pylori antibody levels in urine using a commercially available kit (Rapirun, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan), which utilizes immuno-chromatography, as previously reported [17]. The CYP2C19 genotype was tested using a polymerase chain reaction-restriction fragment length polymorphism assay, as previously reported [18,19,20]. …”

A multicentre randomised trial to compare the efficacy of omeprazole versus rabeprazole in early symptom relief in patients with reflux esophagitis

“…Results from studies in healthy Japanese volunteers suggest that early effects on gastric acid inhibition in people with different CYP2C19 phenotypes may depend on the type of PPI used [ 15 – 17 ]. Compared with omeprazole 20 mg or lansoprazole 30 mg, rabeprazole 10 mg has been shown to exert a faster and more pronounced inhibition of gastric acid secretion in healthy Japanese volunteers with the homoEM or heteroEM phenotypes [ 15 ]; however, in another study also conducted in healthy Japanese volunteers with the homoEM or heteroEM phenotypes, lansoprazole 30 mg was shown to induce an earlier rise in blood PPI concentration and intragastric pH than rabeprazole 10 mg [ 16 ].…”

“…Compared with omeprazole 20 mg or lansoprazole 30 mg, rabeprazole 10 mg has been shown to exert a faster and more pronounced inhibition of gastric acid secretion in healthy Japanese volunteers with the homoEM or heteroEM phenotypes [ 15 ]; however, in another study also conducted in healthy Japanese volunteers with the homoEM or heteroEM phenotypes, lansoprazole 30 mg was shown to induce an earlier rise in blood PPI concentration and intragastric pH than rabeprazole 10 mg [ 16 ]. Furthermore, in healthy Japanese volunteers receiving omeprazole 20 mg or rabeprazole 10 mg, there was no significant difference between the two PPIs in early intragastric pH changes in individuals with the homoEM phenotype, but intragastric pH was significantly higher with omeprazole than with rabeprazole 6–8 h after PPI administration according to combined data from participants with the heteroEM and PM phenotypes [ 17 ]. Thus, whereas the pharmacodynamic and pharmacokinetic profiles of omeprazole and rabeprazole are clearly dependent on CYP2C19 phenotype, data from healthy volunteers on differences in early acid inhibitory effects between the two PPIs are inconsistent.…”