Pharmaceutical Research

, Volume 29, Issue 8, pp 2310–2316 | Cite as

Hydroxylation of R(+)- and S(−)-Omeprazole after Racemic Dosing are Different among the CYP2C19 Genotypes

  • Hideo Shiohira
  • Norio Yasui-Furukori
  • Satoshi Yamada
  • Tomonori Tateishi
  • Yumiko Akamine
  • Tsukasa Uno
Research Paper



To elucidate the stereoselective pharmacokinetics of omeprazole enantiomers and their metabolites after racemic IV dosing because there is little information about the stereoselective metabolism of omeprazole in in vivo study.


Seventeen subjects were classified into three CYP2C19 groups based on their genotypes: homozygous extensive metabolizers (hmEMs; n = 5), heterozygous EMs (htEMs; n = 7) and poor metabolizers (PMs; n = 5).


After single IV administration of racemic omeprazole (20 mg), the mean area under the plasma concentration-time curve (AUC0-∞) of R(+)-omeprazole in PMs was significantly higher than that in hmEMs and htEMs, while that of S(−)-omeprazole was no significance among three genotypes because of a wide inter-individual variability. In addition, although the AUC0-∞ of R(+)-5-hydroxyomeprazole were determined among three genotypes, the that of S(−)-5-hydroxyomeprazole was undetectable in the hmEMs and barely detectable in the htEMs. Conversly, the AUC0-∞ of S(−)-5-hydroxyomeprazole was greater than that of R(+)-5-hydroxyomeprazole in the PMs.


These data therefore suggest that, for EMs, the CYP2C19-mediated formation from R(+)-enantiomer is a 5-hydroxy-metabolite, while that from S(−)-enantiomer may be a minor metabolite. Thus, the in vivo disposition of S(−)- and R(+)-omeprazole after racemic dosing may be different among the CYP2C19 genotypes.


CYP2C19 R(+)-5-hydroxyomeprazole R(+)-omeprazole S(−)-5-hydroxyomeprazole S(−)-omeprazole 



area under the plasma concentration-time curve


maximum plasma concentration


cytochrome P450


homozygous extensive metabolizers


high-performance liquid chromatography


heterozygous extensive metabolizers




elimination rate constant


poor metabolizers


oral administration


proton pump inhibitor


elimination half-life



This works was supported by Grants-in-Aid for Scientific Research (no. 20590150) Tokyo, Japan.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hideo Shiohira
    • 1
  • Norio Yasui-Furukori
    • 2
  • Satoshi Yamada
    • 1
  • Tomonori Tateishi
    • 3
  • Yumiko Akamine
    • 1
  • Tsukasa Uno
    • 1
  1. 1.Department of Hospital PharmacyFaculty of Medicine University of the RyukyusNishihara-choJapan
  2. 2.Department of NeuropsychiatryHirosaki University School of MedicineHirosakiJapan
  3. 3.Pharmaceuticals and Medical Devices AgencyTokyoJapan

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