DICP OpenIR
学科主题物理化学
In Vitro Metabolism of Medroxyprogesterone Acetate with Human Liver Microsome and Comparison with Rat,Minipig Liver Microsmes and Recombinant Human CYP3A4
Zhang JW(张江伟); Liu Y(刘勇); Li W(李巍); Yang L(杨凌)
会议名称The 1st asia Pacific ISSX Meeting
会议日期2006-5-24
2006-05-24
会议地点韩国
页码231/1
部门归属十八室
英文摘要Objective: To study the metabolism of medroxyprogesterone acetate (MPA) in human liver microsomes and compare the metabolim profile with rat, minipig liver mcirosomes and recombinant human CYP3A4. Methods: 100μM MPA was incubated with 0.5mg/ml liver microsomes or recombinant human CYP3A4 for 30 min, the metabolites were analyzed by HPLC and LC/MS/MS. Qualification of each metabolite was performed by the calibration curve of their parent compound MPA. Kinetic parameters were calculated for these main metabolites. Metabolism profiles of MPA by human, rat, minipig liver microsomes and recombinant human CYP3A4 was compared. Results: Five main metabolites (M1, M2, M3, M4, M5) of MPA were isolated by HPLC. Molecular weight was identified by LC-MS to be 418, 402, 402, 402 and 384. The metabolism of MPA was linear in time range of 0-10 min and in human liver microsomes concentration of 0-0.3 mg/ml. Kinetic parameters was calculated, the range of Km was from 7.7 to 11 μM, the range of Vm was from 0.057 to 0.44 nmol/min/mg. Recombinant human CYP3A4, and liver microsomes from human, rat, minipig have rather similar metabolism profiles of MPA though a slight differences were observed. Conclusion: Five main metabolites was found when MPA was metabolized by human liver microsomes. MPA metabolism profiles of recombinant human CYP3A4, liver microsomes from human, rat, and minipig were rather similar. (Supported by the DUT-DICP scientific cooperation fund and the 973 program 2003CB716006 of the Ministry of Science & Technology of China)
语种中文
文献类型会议论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/112186
专题中国科学院大连化学物理研究所
通讯作者Yang L(杨凌)
推荐引用方式
GB/T 7714
Zhang JW,Liu Y,Li W,et al. In Vitro Metabolism of Medroxyprogesterone Acetate with Human Liver Microsome and Comparison with Rat,Minipig Liver Microsmes and Recombinant Human CYP3A4[C],2006:231/1.
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