Improving CYP2C19 phenotyping using stereoselective omeprazole and 5-hydroxy-omeprazole metabolic ratios.

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  • Additional Information
    • Source:
      Publisher: Blackwell Country of Publication: England NLM ID: 101208422 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-7843 (Electronic) Linking ISSN: 17427835 NLM ISO Abbreviation: Basic Clin Pharmacol Toxicol Subsets: MEDLINE
    • Publication Information:
      Publication: <2005-> : Oxford : Blackwell
      Original Publication: Copenhagen, Denmark : Oxford, UK : Nordic Pharmacological Society Distributed by Blackwell Munksgaard, 2004-
    • Subject Terms:
      Omeprazole*/pharmacokinetics ; Cytochrome P-450 CYP2C19*/metabolism ; Cytochrome P-450 CYP2C19*/genetics ; Phenotype* ; Rifampin*/pharmacology ; Fluvoxamine*/pharmacology ; Fluvoxamine*/pharmacokinetics; Humans ; Stereoisomerism ; Male ; Adult ; Female ; Voriconazole/pharmacokinetics ; Young Adult ; Hydroxylation ; Drug Interactions ; Healthy Volunteers ; Proton Pump Inhibitors/chemistry ; Proton Pump Inhibitors/pharmacology ; Proton Pump Inhibitors/pharmacokinetics ; 2-Pyridinylmethylsulfinylbenzimidazoles
    • 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.
      (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
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    • Grant Information:
      SNF 320030_18236 Swiss National Research Foundation
    • Contributed Indexing:
      Keywords: 5‐hydroxy‐omeprazole; CYP2C19; enantiomers; omeprazole; phenotyping
    • Accession Number:
      KG60484QX9 (Omeprazole)
      EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
      EC 1.14.14.1 (CYP2C19 protein, human)
      92340-57-3 (5-hydroxymethylomeprazole)
      VJT6J7R4TR (Rifampin)
      O4L1XPO44W (Fluvoxamine)
      JFU09I87TR (Voriconazole)
      0 (Proton Pump Inhibitors)
      0 (2-Pyridinylmethylsulfinylbenzimidazoles)
    • Publication Date:
      Date Created: 20241010 Date Completed: 20241205 Latest Revision: 20241207
    • Publication Date:
      20241209
    • Accession Number:
      PMC11617642
    • Accession Number:
      10.1111/bcpt.14095
    • Accession Number:
      39385496