Stereoselective Determination of Omeprazole and 5-Hydroxy-Omeprazole in Dried Blood Spots for CYP2C19 Activity Assessment.
5 affiliations
- 1Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden, Netherlands.
- 2Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, Netherlands.
- 3Division of Clinical Pharmacology and Toxicology, Department of Acute Care Medicine, Geneva University Hospitals, Geneva, Switzerland.
- 4Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
- 5School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Geneva, Switzerland.
Abstract
We previously proposed stereoselective 5-hydroxy-omeprazole/omeprazole cut-offs for R- and S-omeprazole to differentiate between rapid, normal, and poor CYP2C19 metabolisers. However, the performance of these stereoselective CYP2C19 phenotyping approaches has never been compared with conventional racemic omeprazole phenotyping. Therefore, dried blood spots from healthy, genetically predicted rapid (n = 15), normal (n = 15), and intermediate (n = 14) CYP2C19 metabolisers were stereoselectively reanalysed after administration of omeprazole alone (10 mg) and following CYP2C19 inhibition with voriconazole (400 mg administered prior to omeprazole). Using stereoselective R-, S-, and racemic 5-hydroxy-omeprazole/omeprazole ratios, CYP2C19 phenotyping performance was assessed by genotype-phenotype concordance and phenoconversion patterns relative to prior reports. An adaptive phenotyping strategy using the 3-h metabolic ratio in individuals with delayed absorption and retaining the 2-h ratio otherwise improved agreement with AUC-based CYP2C19 activity measures (Spearman ρ = 0.99 vs. 0.93 and 0.88 for fixed 2- and 3-h ratios, respectively). Across methods, the racemic approach demonstrated the most favourable overall performance, closely followed by the S-enantiomer-based strategy. In conclusion, while racemic omeprazole phenotyping modestly remains the most accurate strategy for assessing CYP2C19 activity, stereoselective assessment of the S-enantiomer provides an alternative that enables CYP2C19 phenotyping in patients treated with esomeprazole without treatment interruption or substitution with omeprazole.
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BibTeX
@article{hectors2026stereoselective,
title = {{Stereoselective Determination of Omeprazole and 5-Hydroxy-Omeprazole in Dried Blood Spots for CYP2C19 Activity Assessment.}},
author = {Toon Hectors and Kenza Abouir and Emmanuel Varesio and Martijn L Manson and Youssef Daali and Caroline Samer},
journal = {Basic \& clinical pharmacology \& toxicology},
year = {2026},
month = oct,
doi = {10.1111/bcpt.70326},
url = {https://europepmc.org/article/MED/42919487},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Stereoselective Determination of Omeprazole and 5-Hydroxy-Omeprazole in Dried Blood Spots for CYP2C19 Activity Assessment.
AU - Toon Hectors
AU - Kenza Abouir
AU - Emmanuel Varesio
AU - Martijn L Manson
AU - Youssef Daali
AU - Caroline Samer
PY - 2026
DA - 2026/10/30
JO - Basic & clinical pharmacology & toxicology
DO - 10.1111/bcpt.70326
UR - https://europepmc.org/article/MED/42919487
AB - We previously proposed stereoselective 5-hydroxy-omeprazole/omeprazole cut-offs for R- and S-omeprazole to differentiate between rapid, normal, and poor CYP2C19 metabolisers. However, the performance of these stereoselective CYP2C19 phenotyping approaches has never been compared with conventional racemic omeprazole phenotyping. Therefore, dried blood spots from healthy, genetically predicted rapid (n = 15), normal (n = 15), and intermediate (n = 14) CYP2C19 metabolisers were stereoselectively reanalysed after administration of omeprazole alone (10 mg) and following CYP2C19 inhibition with voriconazole (400 mg administered prior to omeprazole). Using stereoselective R-, S-, and racemic 5-hydroxy-omeprazole/omeprazole ratios, CYP2C19 phenotyping performance was assessed by genotype-phenotype concordance and phenoconversion patterns relative to prior reports. An adaptive phenotyping strategy using the 3-h metabolic ratio in individuals with delayed absorption and retaining the 2-h ratio otherwise improved agreement with AUC-based CYP2C19 activity measures (Spearman ρ = 0.99 vs. 0.93 and 0.88 for fixed 2- and 3-h ratios, respectively). Across methods, the racemic approach demonstrated the most favourable overall performance, closely followed by the S-enantiomer-based strategy. In conclusion, while racemic omeprazole phenotyping modestly remains the most accurate strategy for assessing CYP2C19 activity, stereoselective assessment of the S-enantiomer provides an alternative that enables CYP2C19 phenotyping in patients treated with esomeprazole without treatment interruption or substitution with omeprazole.
SN - 1742-7835
SN - 1742-7843
ER -