Work

Improving CYP2C19 phenotyping using stereoselective omeprazole and 5‐hydroxy‐omeprazole metabolic ratios

Year: 2024

Type: article

Abstract: Omeprazole (OME) is a CYP2C19 phenotyping probe, marketed as a racemic (S)/(R) mixture or as an S-enantiomer. Both CYP2C19 and CYP3A4 enzymes mediate (R)-OME hydroxylation to (R)-5-hydroxyomeprazole, while (S)-OME is exclusively hydroxylated via CYP2C19. This study investigates OME and its 5-hydroxymetabolite enantiomers' pharmacokinetics using data from two studies involving healthy volunteers. In Study A, volunteers received OME alone in Session 1, OME combined with voriconazole and fluvoxamine in Session 2 and finally OME with rifampicin in Session 3. In Study B, volunteers received OME alone in Session 1, OME combined with voriconazole in Session 2 and finally OME with fluvoxamine in Session 3. Despite low metabolic ratio values of (S)-OME, detectable modulation of CYP2C19 activity suggests both (R)- and (S)-OME isomers could effectively assess CYP2C19 activity. Further research is needed for precise cut-offs in different phenotype groups.

Source: Basic & Clinical Pharmacology & Toxicology

DOI: 10.1111/bcpt.14095

Authors: Kenza Abouir, Emmanuel Varesio, Julien Déglon, Caroline Samer, Youssef Daali

Institutions: University of Geneva, University Hospital of Geneva, Centre Hospitalier Universitaire Vaudois, University Centre of Legal Medicine

Language: English

Topic: Pharmacogenetics and Drug Metabolism

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,430