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1. Pharm Res. 2012 May 2. [Epub ahead of print]

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

Shiohira H, Yasui-Furukori N, Yamada S, Tateishi T, Akamine Y, Uno T.

Department of Hospital Pharmacy, Faculty of Medicine University of the Ryukyus,
207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.

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.

PMID: 22549736 [PubMed - as supplied by publisher]