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Hydroxylation of R(+)- And S(-)-omeprazole After Racemic Dosing Are Different Among the CYP2C19 Genotypes

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

Pharm Res. 2012 Aug;29(8):2310-6.

PMID: 22549736

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 (AUC(0-∞)) 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 AUC(0-∞) 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 AUC(0-∞) 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP161796776	R-Omeprazole		161796-77-6	Price

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