Abstract
Considering that the genotypes of CYP2C19 and MDR1 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 MDR1 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 MDR1 C3435T for each subject were identified by a direct sequencing method. Statistical analysis was performed in the pharmacokinetic parameters including C max, t 1/2, T max, MRT0–τ, AUC0–2 and AUC0–τ among different genotype groups of CYP2C19 and MDR1 C3435T. Compared to the CYP2C19 EMs, the CYP2C19 PM group showed slower elimination and better oral 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 difference of LSZ in Chinese subjects depends much more on the CYP2C19 polymorphism than on the polymorphism of MDR1 C3435T.
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Acknowledgments
This research was financially supported by A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, 2010, PAPD (TCM combined with western medicine); Leading Talents of scientific research in TCM of Jiangsu Province (No. LJ200906); The National Science and Technology Major Project ‘Creation of Major New Drugs’ (2012ZX09303009-002) from China.
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C. Li and J. Zhang contributed equally to this work.
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Li, CY., Zhang, J., Chu, JH. et al. 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. Eur J Drug Metab Pharmacokinet 39, 121–128 (2014). https://doi.org/10.1007/s13318-013-0148-7
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DOI: https://doi.org/10.1007/s13318-013-0148-7