Pharmacogenomics Associated with Therapy for Acid-Related Disorders

doi:10.1017/CBO9781139051194.019

16 - Pharmacogenomics Associated with Therapy for Acid-Related Disorders

from II - Therapeutic Areas

Published online by Cambridge University Press: 05 June 2012

Edited by

David Flockhart and

Russ B. Altman: Affiliation:
Stanford University, California
David Flockhart: Affiliation:
Indiana University
David B. Goldstein: Affiliation:
Duke University, North Carolina

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Summary

Peptic ulcer and gastroesophageal reflux disease (GERD) are common benign upper gastrointestinal disorders. The major causes of peptic ulcer are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. No matter whether caused by H. pylori, NSAIDs, or both, however, gastric acid plays a markedly important role in the pathogenesis of peptic ulcer. Furthermore, the major cause of GERD is the reflux of gastric acid from the stomach to the esophagus. Gastric acid therefore acts as the most important pathogenic factor of upper gastrointestinal disorders, and acid inhibition with a proton pump inhibitor (PPI) is the major strategy against them. PPIs in combination with one or two antibiotics are also used for the eradication of H. pylori.

PPIs are substitutes of benzimidazole and are mainly metabolized by the cytochrome P450 (CYP) system in the liver (1). The principal enzyme in this metabolism is CYP2C19 (1), although CYP3A4 also plays a role (2–6). Given the presence of interindividual differences in CYP2C19 activity, the pharmacokinetics (PKs) and pharmacodynamics (PDs) of PPIs largely depend on polymorphisms in CYP2C19 (7).

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Type: Chapter
Information: Principles of Pharmacogenetics and Pharmacogenomics , pp. 175 - 187

DOI: https://doi.org/10.1017/CBO9781139051194.019 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2012

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