Hydroxylation of R(+)- and S(-)-Omeprazole after Racemic Dosing are Different among the CYP2C19 Genotypes.
Summary of "Hydroxylation of R(+)- and S(-)-Omeprazole after Racemic Dosing are Different among the CYP2C19 Genotypes."
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.
Affiliation
Department of Hospital Pharmacy, Faculty of Medicine University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.
Journal Details
This article was published in the following journal.
Name: Pharmaceutical research
ISSN: 1573-904X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22549736
- DOI: http://dx.doi.org/10.1007/s11095-012-0757-x
Medical and Biotech [MESH] Definitions
Biomarkers, Pharmacological
Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).
Omeprazole
A highly effective inhibitor of gastric acid secretion used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-EXCHANGING ATPASE) in the proton pump of GASTRIC PARIETAL CELLS.
Dexmedetomidine
A selective inhibitor of RECEPTORS, ADRENERGIC ALPHA-2 that has analgesic and sedative properties. MEDETOMIDINE is the other racemic form.
Levonorgestrel
A synthetic progestational hormone with actions similar to those of PROGESTERONE and about twice as potent as its racemic or (+-)-isomer (NORGESTREL). It is used for contraception, control of menstrual disorders, and treatment of endometriosis.
Sodium Lactate
The sodium salt of racemic or inactive lactic acid. It is a hygroscopic agent used intravenously as a systemic and urinary alkalizer.
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