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

Author(s): Hunfeld NG, Touw DJ, Mathot RA, Mulder PG, VAN Schaik RH, Kuipers EJ, Kooiman JC, Geus WP

Affiliation(s): Central Hospital Pharmacy and Haga Teaching Hospital, Den Haag, The Netherlands.

Publication date & source: 2010-01, Aliment Pharmacol Ther., 31(1):150-9.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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. AIM: 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.

Page last updated: 2010-10-05

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