title: A correlative study of polymorphisms of CYP2C19 and MDR1  C3435T with the pharmacokinetic profiles of lansoprazole and its  main metabolites following single oral administration in healthy  adult Chinese subjects.
abstract: Considering that the genotypes of CYP2C19 and MDRI C3435T are two major factors attributed to the inter-individual pharmacokinetic variability of lansoprazole (LSZ), the aim of the study was to simultaneously elucidate the effects of CYP2C19 and MDRI C3435T polymorphisms on the pharmacokinetics difference of LSZ and its metabolites 5'-hydroxy lansoprazole (HLSZ) and lansoprazole sulphone (LSZS) following oral administration of LSZ tablets in healthy Chinese subjects. Plasma concentration of LSZ, HLSZ and LSZS were quantified by a sensitive and specific LC-MS/MS method, while the genotypes of CYP2C19 and MDRI C3435T for each subject were identified by a direct sequencing method. Statistical analysis was performed in the pharmacokinetic parameters including Cmax, t1/2, Tmax, MRTo_-, AUCO-2 and AUCo_r among different genotype groups of CYP2C 19 and MDRI C3435T. Compared to the CYP2Cl9 EMs, the CYP2C 19 PM group showed slower elimination and betteroral bioavailability of LSZ, much higher plasma concentrations of LSZS and lower concentrations of HLSZ with statistically significance. Despite a tendency of more favorable absorption and rapid elimination of LSZ in wild genotype, no significant pharmacokinetics difference was observed between the wild genotype of MDR1 C3435T and its mutant types. In conclusion, the pharmacokinetics of MDRI C3435T.
authors.forename: Chang-Yin
authors.initials: CY
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Chu
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Xu
authors.forename: Wen-Zheng
authors.initials: WZ
authors.lastname: Ju
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Zou
authors.initials: Z
authors.lastname: Jian-Dong
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
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