title: The (R)-omeprazole hydroxylation index reflects CYP2C19 activity in healthy Japanese volunteers.
abstract: OBJECTIVE
  Omeprazole has (R)- and (S)-enantiomers, which exhibit different pharmacokinetics (PK) among patients with cytochrome P450 (CYP) 2C19 genotype groups. The aim of this study was to investigate whether the 1-point, 4-h postdose (R)-omeprazole hydroxylation index (HI) of racemic omeprazole reflects the three CYP2C19 genotype groups in Japanese individuals.
  
  
  METHODS
  Ninety healthy Japanese individuals were enrolled and classified into the three different CYP2C19 genotype groups: homozygous extensive metabolizers (hmEMs; n = 34), heterozygous EMs (htEMs; n = 44), and poor metabolizers (PMs; n = 12). Blood samples were drawn 4 h after the intake of an oral dose of omeprazole 40 mg, and plasma levels of omeprazole and its metabolites were analyzed by high-performance liquid chromatography (HPLC) using a chiral column.
  
  
  RESULTS
  Mean plasma concentrations of (R)- and (S)-omeprazole in PMs were significantly higher than those in hmEMs and htEMs, and similar results were obtained in the case of omeprazole sulfone. Additionally, there was a significant difference in plasma concentrations of (R)-5-hydroxyomeprazole among CYP2C19 genotype groups, whereas no significant differences were observed in that of (S)-5-hydroxyomeprazole. Similarly, (R)-omeprazole HI in hmEMs, htEMs, and PMs were 5.6, 3.1, and 0.3, respectively, which were significantly different, but no significant difference was present in the (S)-omeprazole HI.
  
  
  CONCLUSIONS
  Our findings demonstrate that (R)-omeprazole HI correlated better with CYP2C19 genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment.
authors: Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.
authors: Satoshi
authors: S
authors: Yamada
authors: Hideo
authors: H
authors: Shiohira
authors: Norio
authors: N
authors: Yasui-Furukori
authors: Tomonori
authors: T
authors: Tateishi
authors: Yumiko
authors: Y
authors: Akamine
authors: Tsukasa
authors: T
authors: Uno
mesh_terms: D000483:Alleles; D000897:Anti-Ulcer Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D065731:Cytochrome P-450 CYP2C19; D016903:Drug Monitoring / Q000379:methods*; D005091:Exons; D056726:Genetic Association Studies; D006801:Humans; D006900:Hydroxylation; D007564:Japan; D050216:Metabolic Detoxication, Phase I; D009853:Omeprazole / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; C040450:omeprazole sulfone; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole