摘要
Abstract
Objective To observe the influences of arecoline hydrobromide (AH) on human hepatic cytochrome P450 activity in vitro by high performance liquid chromatography-mass spectrometry(HPLC-MS)and a cocktail probe substrates method. Methods In this study, six probe substrates of CYP1A2, 2E1, 3A4, 2C9, 2D6 and 2B6 were simultaneously incubated with human liver microsome (HLM) and AH (0-160 μmol/L). The activity of CYP1A2, 2E1, 3A4 and 2C9 was determined by HPLC, and the activity of CYP2D6 and 2B6 was determined by HPLC-MS. Results The activity of CYP2D6, 2B6, 2E1 and 2C9 in HLM was slightly inhibited by AH, which was concentration-dependent. When the AH concentration was 160 μmol/L, the inhibitory rates of the activity of CYP2D6, 2B6, 2E1 and 2C9 in HLM were 36.2%, 38.3%, 35.0% and 35.4%, respectively. Conclusions The risk of metabolic interaction should not be neglected when the substrate drugs of the six kinds of cytochrome P450 isoforms are administered in betelnut addicts.关键词
高效液相/细胞色素P450/人肝微粒体/特异性探针底物/氢溴酸槟榔碱Key words
high performance liquid choromatography (HPLC)/cytochrome P450/human liver microsome/probe substrate/arecoline hydrobromide分类
医药卫生
