Metabolic profiling of praziquantel enantiomers
文献类型：期刊论文
| 作者 | Wang, Haina1,2; Fang, Zhong-Ze2,3,4; Zheng, Yang5; Zhou, Kun3,4,6; Hu, Changyan5; Krausz, Kristopher W.2; Sun, Dequn5; Idle, Jeffrey R.2,7; Gonzalez, Frank J.2 |
| 刊名 | biochemical pharmacology
 |
| 出版日期 | 2014-07-15 |
| 卷号 | 90期号:2页码:166-178 |
| 关键词 | Cytochromes P450 Enantioselective metabolism In silica metabolomics Praziquantel |
| 英文摘要 | praziquantel (pzq), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. in the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (uplc-esi-qtofms) based metabolomics was employed to decipher the metabolic pathways and enantioselective metabolic differences of pzq. many phase i and four new phase ii metabolites were found in urine and feces samples of mice 24 h after dosing, indicating that the major metabolic reactions encompassed oxidation, dehydrogenation, and glucuronidation. differences in the formation of all these metabolites were observed between (r)-pzq and (s)-pzq in an in vitro phase i incubation system, the major involvement of cyp3a, cyp2c9, and cyp2c19 in the metabolism of pzq and cyp3a, cyp2c9, and cyp2c19 exhibited different catalytic activity toward the pzq enantiomers. apparent k-m and v-max differences were observed in the catalytic formation of three mono-oxidized metabolites by cyp2c9 and cyp3a4 further supporting the metabolic differences for pzq enantiomers. molecular docking showed that chirality resulted in differences in substrate location and conformation, which likely accounts for the metabolic differences. in conclusion, in silico, in vitro, and in vivo methods revealed the enantioselective metabolic profile of praziquantel. published by elsevier inc. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | pharmacology & pharmacy |
| 研究领域[WOS] | pharmacology & pharmacy |
| 关键词[WOS] | schistosoma-mansoni ; healthy-volunteers ; acyl glucuronide ; drug-resistance ; efficacy ; stereoselectivity ; pharmacokinetics ; flurbiprofen ; disposition ; inhibition |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000337781700008 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/145885]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Shandong Univ, Coll Pharmaceut Sci, Jinan 250012, Peoples R China 2.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA 3.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China 4.Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China 5.Shandong Univ Weihai, Marine Coll, Weihai 264209, Peoples R China 6.Liaoning Univ Tradit Chinese Med, Coll Pharm, Dept Basic Chem, Dalian 116600, Peoples R China 7.Univ Bern, Dept Clin Res, CH-3010 Bern, Switzerland |
| 推荐引用方式 GB/T 7714 | Wang, Haina,Fang, Zhong-Ze,Zheng, Yang,et al. Metabolic profiling of praziquantel enantiomers[J]. biochemical pharmacology,2014,90(2):166-178. |
| APA | Wang, Haina.,Fang, Zhong-Ze.,Zheng, Yang.,Zhou, Kun.,Hu, Changyan.,...&Gonzalez, Frank J..(2014).Metabolic profiling of praziquantel enantiomers.biochemical pharmacology,90(2),166-178. |
| MLA | Wang, Haina,et al."Metabolic profiling of praziquantel enantiomers".biochemical pharmacology 90.2(2014):166-178. |
入库方式： OAI收割
来源：大连化学物理研究所
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