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人肝脏微粒体在体外对丝裂霉素C的代谢

Metabolism of mitomycin C by human liver microsomes in vitro

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【作者】 郝福荣严敏芬胡卓汉金一尊

【Author】 HAO Fu-rong1,YAN Min-fen 2*,HU Zhuo-han3,JIN Yi-zun2(1.Department of Radiotherapy,Weifang People’s Hospital,Weifang 261000,China;2.Institute of Radiation Medicine,Fudan University,Shanghai 200032,China;3.Ruld Research Institute for Liver Diseases,Shanghai 201203,China)

【机构】 潍坊市人民医院放疗科复旦大学放射医学研究所瑞德肝脏疾病研究所复旦大学放射医学研究所 山东潍坊261000上海200032上海201203

【Abstract】 Aim To provide the profiles of metabolism of mitomycin C(MMC)by human liver microsomes in vitro,MMC was incubated with human liver microsomes,then the supernatant component was isolated and detected by HPLC.Types of metabolic enzymes were estimated by the effect of NADPH or dicumarol(DIC)on metabolism of MMC.Standard,reaction,background control(microsomes was inactivated),negative control(no NADPH),and inhibitor group(adding DIC)were assigned,the results were analyzed by Graphpad Prism 4.0 software.Reaction group compared with background control and negative control groups,3 NADPH-dependent absorption peaks were additionally isolated by HPLC after MMC were incubated with human liver microsomes.Their retention times were 10.0,14.0,14.8 min(named as M1,M2,M3),respectively.Their formation was kept as Sigmoidal dose-response and their K_m were 0.52(95% CI,0.40-0.67)mmol·L-1,0.81(95% CI,0.59-1.10)mmol·L-1,0.54(95% CI,0.41-0.71)mmol·L-1,respectively.The data indicated that the three absorption peaks isolated by HPLC were metabolites of MMC.DIC can inhibit formation of M2,it’s dose-effect fitted to Sigmoidal curve and it’s IC_ 50 was 59.68(95% CI,40.66-87.61)μmol·L-1,which indicated DT-diaphorase could take part in the formation of M2.MMC can be metabolized by human liver microsomes in vitro,and at least three metabolites of MMC could be isolated by HPLC in the experiment,further study showed DT-diaphorase participated in the formation of M2.

【关键词】 丝裂霉素药代动力学微粒体,肝HPLC
【Key words】 mitomycinpharmacokineticsmicrosomes,liverHPLC
【基金】 国家自然科学基金资助项目(30400089)
  • 【文献出处】 药学学报 ,Acta Pharmaceutica Sinica , 编辑部邮箱 ,2007年02期
  • 【分类号】R96
  • 【被引频次】1
  • 【下载频次】196
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