Tags

Type your tag names separated by a space and hit enter

Esomeprazole Therapy and CYP2C19 Genotype

Abstract
Esomeprazole (brand name Nexium) is a proton pump inhibitor (PPI) used to treat gastroesophageal reflux disease (GERD) and to reduce the risk of gastric ulcers associated with nonsteroidal anti-inflammatory drug NSAID use. Esomeprazole is also used in the treatment of hypersecretory conditions, such as Zollinger-Ellison syndrome, and in combination with antibiotics to eradicate Helicobacter pylori (H. pylori) infection. Esomeprazole reduces the acidity (raises the pH) in the stomach by inhibiting the secretion of gastric acid. The level of esomeprazole an individual is exposed to is influenced by several factors, such as the dose used and how quickly the drug is metabolized and inactivated. Esomeprazole is primarily metabolized by the CYP2C19 enzyme. Individuals with increased CYP2C19 enzyme activity (“CYP2C19 ultrarapid metabolizers”) may have an insufficient response to standard doses of esomeprazole, because the drug is inactivated at a faster rate. In contrast, individuals who have reduced or absent CYP2C19 enzyme activity (i.e., CYP2C19 intermediate and poor metabolizers) have a greater exposure to esomeprazole. The 2018 FDA-approved drug label for esomeprazole states that 3% of Caucasians, and 15–20% of Asians are CYP2C19 poor metabolizers, and that poor metabolizers have approximately twice the level of exposure to esomeprazole, compared with CYP2C19 normal metabolizers. However, the drug label does not include dosing recommendations for CYP2C19 poor metabolizers (1). Esomeprazole recommendations have been published by the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), which indicates that no change in dosing is recommended for CYP2C19 poor, intermediate, or ultrarapid metabolizers. The DPWG states that although genetic variation in CYP2C19 influences the plasma concentration of esomeprazole, there is insufficient evidence to support an effect on treatment outcomes or side effects (2).

Authors

Director, Pharmacogenomics and Molecular Genetics Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Bloomington, IN 47405Medical Director, The DeBartolo Family Personalized Medicine Institute, Senior Member, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL 33612Division Director, Clinical Data Management and Curation, CancerLinQ LLC, Alexandria, VAAssociate Professor, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Division Head, Pharmacogenomics, Sema4, Stanford, CT 06902Senior Medical Writer, Medical Genetics and Human Variation, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894Chief, Medical Genetics and Human Variation, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894Project Lead, Medical Genetics and Human Variation, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894

Publisher

National Center for Biotechnology Information (US)
Bethesda (MD)

Language

eng

PubMed ID

28520354

Citation

Dean L: Esomeprazole Therapy and CYP2C19 Genotype. Medical Genetics Summaries. Edited by Pratt VM, et al: National Center for Biotechnology Information (US), 2012, Bethesda (MD).
Dean L. Esomeprazole Therapy and CYP2C19 Genotype. Edited by Pratt VM, McLeod HL, Rubinstein WS, et al. Medical Genetics Summaries. National Center for Biotechnology Information (US); 2012.
Dean L. (2012). Esomeprazole Therapy and CYP2C19 Genotype. Edited by Pratt VM & McLeod HL & Rubinstein WS, et al. In Medical Genetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US)
Dean L. Esomeprazole Therapy and CYP2C19 Genotype. Edited by Pratt VM, et al. Medical Genetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
* Article titles in AMA citation format should be in sentence-case
TY - CHAP T1 - Esomeprazole Therapy and CYP2C19 Genotype BT - Medical Genetics Summaries A1 - Dean,Laura, Y1 - 2012/// PY - 2019/9/23/pubmed PY - 2019/9/23/medline PY - 2017/5/19/entrez KW - Esomeprazole therapy KW - Nexium KW - Nexium response KW - CYP2C19 KW - ulcer KW - GERD KW - reflux N2 - Esomeprazole (brand name Nexium) is a proton pump inhibitor (PPI) used to treat gastroesophageal reflux disease (GERD) and to reduce the risk of gastric ulcers associated with nonsteroidal anti-inflammatory drug NSAID use. Esomeprazole is also used in the treatment of hypersecretory conditions, such as Zollinger-Ellison syndrome, and in combination with antibiotics to eradicate Helicobacter pylori (H. pylori) infection. Esomeprazole reduces the acidity (raises the pH) in the stomach by inhibiting the secretion of gastric acid. The level of esomeprazole an individual is exposed to is influenced by several factors, such as the dose used and how quickly the drug is metabolized and inactivated. Esomeprazole is primarily metabolized by the CYP2C19 enzyme. Individuals with increased CYP2C19 enzyme activity (“CYP2C19 ultrarapid metabolizers”) may have an insufficient response to standard doses of esomeprazole, because the drug is inactivated at a faster rate. In contrast, individuals who have reduced or absent CYP2C19 enzyme activity (i.e., CYP2C19 intermediate and poor metabolizers) have a greater exposure to esomeprazole. The 2018 FDA-approved drug label for esomeprazole states that 3% of Caucasians, and 15–20% of Asians are CYP2C19 poor metabolizers, and that poor metabolizers have approximately twice the level of exposure to esomeprazole, compared with CYP2C19 normal metabolizers. However, the drug label does not include dosing recommendations for CYP2C19 poor metabolizers (1). Esomeprazole recommendations have been published by the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), which indicates that no change in dosing is recommended for CYP2C19 poor, intermediate, or ultrarapid metabolizers. The DPWG states that although genetic variation in CYP2C19 influences the plasma concentration of esomeprazole, there is insufficient evidence to support an effect on treatment outcomes or side effects (2). PB - National Center for Biotechnology Information (US) CY - Bethesda (MD) UR - https://www.unboundmedicine.com/medline/citation/28520354/Medical_Genetics_Summaries:_Esomeprazole_Therapy_and_CYP2C19_Genotype L2 - https://www.ncbi.nlm.nih.gov/books/NBK100896 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.