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

作　　者：郝福荣[1] 严敏芬[2] 胡卓汉 金一尊[2] 

机构地区：[1]潍坊市人民医院放疗科,山东潍坊261000 [2]复旦大学放射医学研究所,上海200032 [3]瑞德肝脏疾病研究所,上海201203

出　　处：《药学学报》2007年第2期221-225,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30400089)

摘　　要：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.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 supematant 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 analyzed by Graphpad Prism 4.0 software. Reaction group compared with background control results were 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 Km 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 IC50 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 

分 类 号：R969[医药卫生—药理学]