title: Determination of R(+)- and S(-)-lansoprazole using chiral stationary-phase liquid chromatography and their enantioselective pharmacokinetics in humans.
abstract: OBJECTIVE
  Stereoselective and sensitive methods employing chiral stationary phase columns for HPLC determination of enantiomers of lansoprazole in the human serum were developed and pharmacokinetic behaviors of the enantiomers were evaluated in seven subjects.
  
  
  METHODS
  Five chiral stationary phase columns: Chiralcel OD (cellulose tris(3,5-dimethyl-phenylcarbamate)), OF (cellulose tris(4-chlorophenylcarbamate)), OG (cellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methylbenzoate)), and Chiralpak AS (amylose tris ((S)-1-phenylethylcarbamate)) were investigated.
  
  
  RESULTS
  Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(-)-enantiomers from racemic lansoprazole, but Chiralcel OF, OG, and OJ did not. The mean Cmax and the AUC values of R(+)-enantiomer were 3-5 times greater than those of S(-)-enantiomer following oral administration of 30 mg of racemic lansoprazole. The CLtot values of R(+)-enantiomer were significantly smaller than those of S(-)-enantiomer. Binding of R(+)-enantiomer to human serum proteins was significantly greater than that of S(-)-enantiomer. The mean metabolic ratio (metabolites/parent compound) in human liver microsomes of S(-)-enantiomer was significantly greater than that of R(+)-enantiomer.
  
  
  CONCLUSIONS
  The stereoselective pharmacokinetics of lansoprazole enantiomers is likely due to its stereoselective protein binding and/or metabolism.
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Katsuki
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.forename: K
authors.initials: K
authors.lastname: Arimori
authors.forename: C
authors.initials: C
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Katafuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujioka
authors.forename: S
authors.initials: S
authors.lastname: Fujiyama
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding; D054328:Proton Pump Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013607:Tablets
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001798:Blood Proteins; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013607:Tablets; D064747:Lansoprazole; D009853:Omeprazole