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1. Aliment Pharmacol Ther. 2012 Feb 13. doi: 10.1111/j.1365-2036.2012.05014.x. [Epub
ahead of print]

A comparison of the acid-inhibitory effects of esomeprazole and rabeprazole in
relation to pharmacokinetics and CYP2C19 polymorphism.

Hunfeld NG, Touw DJ, Mathot RA, van Schaik RH, Kuipers EJ.

Department of Hospital Pharmacy, Central Hospital Pharmacy, Haga Teaching
Hospital, Den Haag, The Netherlands.

BACKGROUND: Esomeprazole and rabeprazole are metabolised in the liver by means of
the CYP2C19 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 PPIs 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 CYP2C19 genotype and pharmacokinetics. METHODS: Eighteen
healthy Helicobacter pylori-negative Caucasian subjects with CYP2C19*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 CYP2C19 polymorphism.

© 2012 Blackwell Publishing Ltd.

PMID: 22324425 [PubMed - as supplied by publisher]