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Updated: May 29, 2026
12:21
Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
Published on: November 27, 2016
CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP
Patricia Huezo-Diaz1, Nader Perroud, Edgar P Spencer
1MRC SGDP Centre, Institute of Psychiatry at King's College London, London, UK.
Journal of Psychopharmacology (Oxford, England)
|September 20, 2011
Summary
Genetic variations in CYP2C19 influence escitalopram levels. Specifically, CYP2C19 ultrarapid metabolizers had lower drug concentrations, while poor metabolizers had higher concentrations, impacting depression treatment.
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Metabolism Studies
Background:
- Cytochrome P450 enzymes, specifically CYP2C19 and CYP2D6, are known to metabolize escitalopram.
- Understanding the impact of genetic variations on drug metabolism is crucial for personalized medicine.
Purpose of the Study:
- To investigate the effect of CYP2C19 and CYP2D6 genotypes on escitalopram and its metabolite, N-desmethylescitalopram, concentrations.
- To determine the relationship between genetic variations and the metabolic ratio of escitalopram in patients with depression.
Main Methods:
- Analysis of CYP2C19 and CYP2D6 genotypes in 196 adult patients with depression from the GENDEP pharmacogenomic trial.
- Measurement of steady-state morning concentrations of escitalopram and N-desmethylescitalopram.
- Statistical analysis to correlate genotypes with drug concentrations and metabolic ratios, controlling for age and CYP2D6 status.
Main Results:
- CYP2D6 intermediate/poor metabolizers showed higher escitalopram concentrations compared to extensive metabolizers.
- Individuals homozygous for the CYP2C19*17 ultrarapid metabolizer allele had significantly lower escitalopram concentrations (2-fold) and higher metabolic ratios.
- Homozygosity for CYP2C19 poor metabolizer alleles was associated with higher escitalopram concentrations (1.55-fold).
- A significant association was found between CYP2C19 genotypic category and escitalopram concentration.
Conclusions:
- CYP2C19 genotype significantly impacts steady-state escitalopram concentrations.
- The CYP2C19*17 allele, associated with ultrarapid metabolism, leads to reduced escitalopram levels.
- Genetic testing for CYP2C19 may aid in optimizing escitalopram dosing for patients with depression.
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