Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects

Abstract

1. The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5′-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ.

2. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method.

3. After single i.v. doses of 15, 30 and 60 mg LPZ, C_max and area under the plasma concentration-time curve (AUC_0-t) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg·L⁻¹ and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg·h·L⁻¹, respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15–60 mg.

4. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

Keywords::

• Lansoprazole
• 5′-hydroxy lansoprazole
• lansoprazole sulphone
• pharmacokinetics
• intravenous infusion
• Chinese subjects
• CYP2C19 phenotyping