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


OBJECTIVE
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.
Department of Hospital Pharmacy, Central Hospital Pharmacy, Haga Teaching Hospital, Den Haag, The Netherlands. n.hunfeld@erasmusmc.nl
N G
NG
Hunfeld
D J
DJ
Touw
R A
RA
Mathot
R H
RH
van Schaik
E J
EJ
Kuipers
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064098:Esomeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008962:Models, Theoretical; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064750:Rabeprazole; D044465:White People / Q000235:genetics*; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole