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

• Published in: Alimentary pharmacology & therapeutics Vol. 31; no. 1; pp. 150 - 159
• Main Authors: HUNFELD, N. G., TOUW, D. J., MATHOT, R. A., MULDER, P. G. H., VAN SCHAIK, R. H., KUIPERS, E. J., KOOIMAN, J. C., GEUS, W. P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2010
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - administration & dosage; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; Adolescent; Adult; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - pharmacokinetics; Aryl Hydrocarbon Hydroxylases - drug effects; Aryl Hydrocarbon Hydroxylases - genetics; Cytochrome P-450 CYP2C19; Esomeprazole - administration & dosage; Esomeprazole - pharmacokinetics; Female; Gastric Acid - metabolism; Gastric Acid - secretion; Gastric Acidity Determination; Genotype; Helicobacter Infections - genetics; Helicobacter Infections - metabolism; Helicobacter pylori; Humans; Male; Monitoring, Physiologic; Polymorphism, Genetic - drug effects; Time Factors; Treatment Outcome; Young Adult
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2009.04150.x

Summary 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.