CYP2C19 Polymorphism and Proton Pump Inhibitors

Authors

  • Ulrich Klotz,

    Corresponding author
    1. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, D-70376 Stuttgart, and
    • Author for correspondence: Ulrich Klotz, Dr. Margarete Fischer-Bosch-Institut of Clinical Pharmakology, Auerbachstraße 112, D-70376 Stuttgart, Germany (fax +0049 (711) 859295, e-mail ulrich.klotz@ikp-stuttgart.de).

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  • Matthias Schwab,

    1. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, D-70376 Stuttgart, and
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  • Gerhard Treiber

    1. Department of Gastroenterology and Hepatology, University Hospital of Magdeburg, Leipziger Str. 144, D-39120 Magdeburg, Germany
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Abstract

Abstract: Proton pump inhibitors such as omeprazole (esomeprazole), lansoprazole, pantoprazole and rabeprazole are eliminated by the hepatic route and the polymorphic CYP2C19 is mainly involved in their metabolism. In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5–12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors.

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