A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism.
BACKGROUND
Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs.


OBJECTIVE
To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics.


METHODS
CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing.


RESULTS
A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5.


CONCLUSIONS
Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.
Central Hospital Pharmacy and Haga Teaching Hospital, Den Haag, The Netherlands.
N G
NG
Hunfeld
D J
DJ
Touw
R A
RA
Mathot
P G H
PG
Mulder
R H
RH
VAN Schaik
E J
EJ
Kuipers
J C
JC
Kooiman
W P
WP
Geus
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects* / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D000077402:Pantoprazole; D011110:Polymorphism, Genetic / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole