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

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.