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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

ABSTRACT

Purpose

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.

Methods

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).

Results

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.

Conclusions

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.

KEY WORDS

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

ABBREVIATIONS

AUC

area under the plasma concentration-time curve

Cmax

maximum plasma concentration

CYP

cytochrome P450

hmEMs

homozygous extensive metabolizers

HPLC

high-performance liquid chromatography

htEMs

heterozygous extensive metabolizers

IV

intravenous

ke

elimination rate constant

PMs

poor metabolizers

PO

oral administration

PPI

proton pump inhibitor

t1/2

elimination half-life

Notes

ACKNOWLEDGMENTS & DISCLOSURES

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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