title: Effects of CYP2C19 polymorphism on the pharmacokinetics of lansoprazole and its main metabolites in healthy Chinese subjects.
abstract: The aim of the study was to determine the pharmacokinetics of lansoprazole and its main metabolites (5'-hydroxy lansoprazole and lansoprazole sulphone) after administration of enteric-coated tablet in healthy Chinese subjects classified by CYP2C19 genotypes, and evaluate the effects of CYP2C19 genotypes on the pharmacokinetics of the three compounds. A single oral dose of 30 mg lansoprazole was administrated to 24 healthy Chinese male volunteers in different CYP2C19 genotype groups. Blood samples were collected from pre-dose up to 14-h post-dose. Plasma concentration of lansoprazole and its main metabolites were quantified by liquid chromatography-tandem mass spectrometry. CYP2C19 polymorphism had significant effects on the pharmacokinetics of lansoprazole and its main metabolites. The differences in the pharmacokinetics between CYP2C19 extensive metabolizers (Ems) (homo-EMs and hete-EMs) and PMs were more significant for lansoprazole sulphone than for 5'-hydroxy lansoprazole. The results indicate that the monitoring of lansoprazole and its main metabolites in plasma at the time-points in the elimination phase for lansoprazole could reflect the activity of CYP2C19. Simultaneously monitored with lansoprazole sulphone, lansoprazole might be a useful probe drug for CYP2C19.
authors.affiliation: Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.forename: Guocai
authors.initials: G
authors.lastname: Wang
authors.forename: Huichen
authors.initials: H
authors.lastname: Liu
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002681:China; D065731:Cytochrome P-450 CYP2C19; D006801:Humans; D064747:Lansoprazole; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; C581535:Lansoprazole Sulfone; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; C498264:5-hydroxylansoprazole