title: Hydroxylation of R(+)- and S(-)-omeprazole after racemic dosing are different among the CYP2C19 genotypes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine University of Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shiohira
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tateishi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Akamine
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D009853:Omeprazole / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole