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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing.
John J Lima1, Cameron D Thomas2, Julia Barbarino3
1Center for Pharmacogenomics and Translational Research, Nemours Children's Health, Jacksonville, Florida, USA.
Clinical Pharmacology and Therapeutics
|August 10, 2020
Summary
Genetic testing for CYP2C19 genotype can personalize proton pump inhibitor (PPI) therapy. This approach optimizes PPI dosing for improved efficacy and reduced toxicity in patients.
Area of Science:
- Pharmacogenomics
- Gastroenterology
Background:
- Proton pump inhibitors (PPIs) are essential for managing acid-related disorders.
- Most PPIs undergo metabolism via cytochrome P450 2C19 (CYP2C19).
- CYP2C19 genotype influences PPI pharmacokinetics, efficacy, and safety.
Purpose of the Study:
- To review existing literature on CYP2C19 genotype and PPIs.
- To provide evidence-based recommendations for genotype-guided PPI prescribing.
- To enhance therapeutic outcomes and minimize adverse events.
Main Methods:
- Literature review and evidence synthesis.
- Analysis of studies linking CYP2C19 genotype to PPI exposure and clinical outcomes.
- Development of clinical practice guidelines.
Main Results:
- CYP2C19 genotype predicts variable PPI plasma concentrations.
- Genotypes associated with lower exposure may require higher PPI doses for efficacy.
- Genotypes associated with higher exposure may benefit from lower PPI doses to reduce toxicity.
Conclusions:
- CYP2C19 genotyping offers a valuable tool for optimizing PPI therapy.
- Personalized dosing based on genotype can improve treatment effectiveness.
- Genotype-guided therapy can mitigate risks of long-term PPI use, especially at high concentrations.
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