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

Abstract

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. 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. 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. 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.

Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods

“…Quantification of lansoprazole and its main metabolites in plasma. Concentrations for lansoprazole and metabolites will be quantified using liquid chromatography/mass spectroscopy as described [46,47]. This method is more sensitive than high performance liquid chromatography for metabolites requiring less plasma or blood.…”

Effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites in rats

“…CYP2C19 is polymorphic, which has significant effects on the pharmacokinetics of lansoprazole and its metabolites. The differences in pharmacokinetics between CYP2C19 extensive metabolizers and poor metabolizers are more significant for lansoprazole sulfone than for 5-hydroxylansoprazole (Zhang et al, 2012). Therefore, any food components metabolized by CYP2C19 or CYP3A, especially those that affect CYPs, may influence the pharmacokinetics of lansoprazole in vivo (Saito et al, 2005).…”

Application of nanoparticles for oral delivery of acid-labile lansoprazole in the treatment of gastric ulcer: in vitro and in vivo evaluations

“…Determined amount of drug in nanoparticles Total a = m mount of drug used for nanoparticles preparation × 100% (2) In vitro drug release LPZ-loaded nanoparticles were suspended in 5 mL of phosphate-buffered solution (pH 7.4) which was placed in a dialysis bag (molecular weight cutoff 6,000-8,000 Da) followed by immersion in 100 mL of the same release medium at 37°C±0.5°C in a shaker bath at 75 rpm. Samples (1 mL) were collected at time intervals of 0.…”

“…The HPLC analytical method was validated prior to sample analysis. Drug loading (DL) and encapsulation efficiency (EE) were calculated using equations (1) and (2).…”

“…The mechanism of action of proton pump inhibitors is via selective inhibition of H + /K + ATPase (also known as a the proton pump), an enzyme system present in gastric parietal cells, to suppress secretion of gastric acid and promote ulcer healing activity in patients. 2 Lansoprazole (LPZ) is a proton pump inhibitor. It is metabolized in the parietal cells to form an active sulfonamide metabolite that inactivates the sulfhydryl group of the proton pump, thereby reducing hydrogen ion secretion.…”