title: Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19.
abstract: OBJECTIVE
  To evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19.
  
  
  METHODS
  A single oral dose of racemic lansoprazole (30 mg) was administered to 6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction-restriction fragment length polymorphism. The pharmacokinetic parameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration. The unbound fraction of lansoprazole enantiomers was determined by means of ultrafiltration of fresh human serum spiked with racemic lansoprazole.
  
  
  RESULTS
  The plasma concentrations of R(+)-lansoprazole were consistently higher than those of the S(-)-enantiomer in both extensive and poor metabolizers of CYP2C19, and the mean area under the plasma concentration-time curve of the (+)- and (-)-enantiomers showed 4.3- and 5.8-fold differences between poor and extensive metabolizers, respectively. The (+)/(-) ratios of lansoprazole clearance were not significantly different between poor and extensive metabolizers (0.19 +/- 0.07 and 0.05 +/- 0.08, respectively). The values for volume of distribution of the (-)-enantiomer were 3- and 10-fold greater, respectively, than those of the (+)-enantiomer in poor and extensive metabolizers, which was related to a 2-fold higher unbound fraction of the (-)-enantiomer.
  
  
  CONCLUSIONS
  The effect of CYP2C19 genetic polymorphism on the enantioselective disposition of lansoprazole seems to be less significant than the effect on omeprazole and pantoprazole. The disposition of lansoprazole enantiomers appears to be influenced by enantioselective protein binding and by enantioselective metabolism of lansoprazole.
authors.affiliation: Department of Pharmacology, Inje University College of Medicine and Clinical Pharmacology Center, Pusan Paik Hospital, and the Department of Chemistry, Pusan National University, Pusan, South Korea.
authors.forename: Kyoung-Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shon
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Doo-Hee
authors.initials: DH
authors.lastname: Yun
authors.forename: Moon-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: In-June
authors.initials: IJ
authors.lastname: Cha
authors.forename: Myung-Ho
authors.initials: MH
authors.lastname: Hyun
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000465:Algorithms; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D001711:Biotransformation; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D064748:Dexlansoprazole; D005260:Female; D006207:Half-Life; D006801:Humans; D007723:Korea; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D064748:Dexlansoprazole