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16 - Pharmacogenomics Associated with Therapy for Acid-Related Disorders
from II - Therapeutic Areas
Published online by Cambridge University Press: 05 June 2012
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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- Principles of Pharmacogenetics and Pharmacogenomics , pp. 175 - 187Publisher: Cambridge University PressPrint publication year: 2012