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A comparison of the acid‐inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP 2 C 19 polymorphism
Author(s) -
Hunfeld N. G.,
Touw D. J.,
Mathot R. A.,
Schaik R. H.,
Kuipers E. J.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2012.05014.x
Subject(s) - esomeprazole , rabeprazole , cyp2c19 , pharmacology , pharmacokinetics , medicine , crossover study , omeprazole , dosing , genotype , gastroenterology , gastric acid , helicobacter pylori , pharmacodynamics , chemistry , stomach , biochemistry , placebo , metabolism , alternative medicine , cytochrome p450 , pathology , gene
Summary Background Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP 2 C 19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25–30% an intermediate and 2–5% a slow metaboliser phenotype. It is unknown whether different PPI s are affected to the same extent by these phenotypic differences. Aim To compare the acid‐inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP 2 C 19 genotype and pharmacokinetics. Methods Eighteen healthy H elicobacter pylori ‐negative C aucasian subjects with CYP2C 19*2‐*6 and *17 genotype were included in a randomised investigator‐blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24‐h pH ‐monitoring was performed on days 0, 1 and 5 of oral dosing. Results Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH : day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P < 0.001; percentage of time pH >4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P < 0.001). Differences in acid inhibition between wt/wt and wt/*2 genotype were significant for both PPIs . Conclusions Once‐daily dosing with esomeprazole 40 mg provides a more effective and faster acid‐inhibitory effect than rabeprazole 20 mg. The acid‐inhibitory effect of esomeprazole and rabeprazole are both influenced by CYP 2 C 19 polymorphism.