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学科主题物理化学
Metabolic profiling and P450 phenotyping of medroxyprogesterone acetate
Zhang JW(张江伟); Hu ZH(胡卓汉); Ge GB(葛广波); Liu Y(刘勇); Liu HT(刘洪涛); Li W(李巍); Liu HX(刘慧鑫); Zhang YY(张延延); Yang L(杨凌)
会议名称2nd ASIAN PACIFIC REGIONAL ISSX MEETING
会议日期2008-5-11
2008-05-11
会议地点中国
页码132/1
部门归属十八室
主办者DRUG METABOLISM REVIEWS
英文摘要Medroxyprogesterone acetate (MPA) is one of the most frequently prescribed progestin for clinical conception, hormone replacement therapy, and adjuvant endocrine therapy. MPA has a low oral bioavailability due to extensive metabolism. However, MPA metabolism was poorly documented. This study was intended to profile the phase I metabolites of MPA and the P450 isoforms involved. After MPA was incubated with human liver microsomes and NADPH-generating system, five main metabolites (namely M-1, M-2, M-3, M-4, and M-5) were isolated by HPLC. Three major metabolites (M-2, M-4 and M-3) were tentatively identified to be 6β-, 2β-, and 1β- hydroxy MPA by LC/MS and 1HNMR. By consecutive metabolism of purified M-2, M-3 and M-4, M-1 and M-5 were proposed to be 2β-, 6β-dihydroxy MPA and 1-dehydro MPA, respectively. CYP3A4 was identified to be the isoform primarily involved in the formation of M-2 to M-5 in studies using specific inhibitors, recombinant P450s, and correlation comparisons. Rat and minipig liver microsomes were included to evaluate species differences, and the results showed little difference among the species. In conclusion, CYP3A4 was the major CYP isoform involved in MPA hydroxylation, with 6β-, 2β-, and 1β- being the preferred hydroxylation sites. Minipig and rat could be the surrogate models for man in MPA pharmacokinetic /script>
语种中文
WOS记录号WOS:000265257500196
引用统计
文献类型会议论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/113480
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,Hu ZH,Ge GB,et al. Metabolic profiling and P450 phenotyping of medroxyprogesterone acetate[C],2008:132/1.
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