Zhang Dan, Wang Xiaolin, Yang Man, Wang Guocai, Liu Huichen
Department of Clinical Pharmacology, Aerospace Center Hospital, Beijing, PR China.
Xenobiotica. 2011 Jun;41(6):511-7. doi: 10.3109/00498254.2011.559556. Epub 2011 Apr 27.
The aim of the study was to determine the pharmacokinetics of lansoprazole and its main metabolites (5'-hydroxy lansoprazole and lansoprazole sulphone) after administration of enteric-coated tablet in healthy Chinese subjects classified by CYP2C19 genotypes, and evaluate the effects of CYP2C19 genotypes on the pharmacokinetics of the three compounds. A single oral dose of 30 mg lansoprazole was administrated to 24 healthy Chinese male volunteers in different CYP2C19 genotype groups. Blood samples were collected from pre-dose up to 14-h post-dose. Plasma concentration of lansoprazole and its main metabolites were quantified by liquid chromatography-tandem mass spectrometry. CYP2C19 polymorphism had significant effects on the pharmacokinetics of lansoprazole and its main metabolites. The differences in the pharmacokinetics between CYP2C19 extensive metabolizers (Ems) (homo-EMs and hete-EMs) and PMs were more significant for lansoprazole sulphone than for 5'-hydroxy lansoprazole. The results indicate that the monitoring of lansoprazole and its main metabolites in plasma at the time-points in the elimination phase for lansoprazole could reflect the activity of CYP2C19. Simultaneously monitored with lansoprazole sulphone, lansoprazole might be a useful probe drug for CYP2C19.
本研究的目的是确定在按CYP2C19基因型分类的健康中国受试者中，服用肠溶衣片后兰索拉唑及其主要代谢产物（5'-羟基兰索拉唑和兰索拉唑砜）的药代动力学，并评估CYP2C19基因型对这三种化合物药代动力学的影响。对24名不同CYP2C19基因型组的健康中国男性志愿者单次口服30 mg兰索拉唑。在给药前至给药后14小时采集血样。采用液相色谱-串联质谱法定量测定兰索拉唑及其主要代谢产物的血浆浓度。CYP2C19基因多态性对兰索拉唑及其主要代谢产物的药代动力学有显著影响。兰索拉唑砜在CYP2C19广泛代谢者（EMs，包括纯合子EMs和杂合子EMs）和PMs之间的药代动力学差异比5'-羟基兰索拉唑更显著。结果表明，在兰索拉唑消除相的时间点监测血浆中兰索拉唑及其主要代谢产物可以反映CYP2C19的活性。与兰索拉唑砜同时监测时，兰索拉唑可能是一种有用的CYP2C19探针药物。
