title: Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects.
abstract: The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.
authors.affiliation: Department of Clinical Pharmacology, Aerospace Center Hospital, 15 Yuquan Road, Haidian District, 100049, Beijing, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Man
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Huichen
authors.initials: H
authors.lastname: Liu
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D064747:Lansoprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; C581535:Lansoprazole Sulfone; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C498264:5-hydroxylansoprazole