体内代谢法研究新药对细胞色素P450 1A2和2E1的影响  

Effects of new drun metabolism on CYP1A2 and CYP2E1

作　　者：石杰[1] 王本坚[1] 杨旭[1] 

机构地区：[1]青岛市立医院药物研究室,山东266071

出　　处：《肝脏》2008年第5期387-389,417,共4页Chinese Hepatology

摘　　要：目的研究新药对大鼠肝药酶的影响及其性别差异,从而对这些新药进行安全性评价。方法通过研究肝药酶细胞色素P450(CYP)1A2和CYP2E1的专属探针药物咖啡因和氯唑沙宗在对照组与给药组的体内代谢过程的变化,判断药物对这些酶有无诱导或抑制作用。结果新药SPMG对CYP1A2和CYP2E1均无影响,AOSC对CYP1A2无影响,但对雄性大鼠的CYP2E1有诱导作用。GC对雌性大鼠的CYP1A2有抑制作用而对雄性大鼠的CYP2E1有明显的诱导作用。结论药物对CYP各亚酶的影响存在明显的性别差异,AOSC和GC在与各种与CYP 1A2和/或CYP 2E1代谢有关的药物合用时,应充分考虑其在不同性别间的差异,以避免潜在的毒性或不良反应。而SPMG在此情况下则相对安全。Objective The effects of new drug metabolism on CYP1 A2 and CYP2E1 were studied and the drugs safety assessment of this drugs were evaluated. Methods The metabolic changes of the Caffeine and Chlorzoxazone probed to respectively were studied in vivo, then the inhibitory or induced effects of these new drugs on CYPIA2 or CYP2E1 were evaluated. Results Sulfated polymannuroguluronate （SPMG） had no effect on CYP1A2 and 2E1 ; Acidic oligosaecharide sugar chain compound （AOSC） had no effect on CYPI A2 while it can induced the CYP2E1 on male rats; Cheliensisin A （GC） can inhibit CYPIA2 on female rats while induced CYP2E1 on male rats. Conclusion Different drugs has different effect on CYP subtype enzymes and these effect had a sex-based difference. When AOSC and GC are used combined with other drugs which are related with CYP1 A2 and CYP2E1 enzymes, the different effects of these drugs on it should be considered totally to avoid the potential toxicities or side-effects. SPMG are relatively safe.

关 键 词：新药 安全性预测 咖啡因 氯唑沙宗 细胞色素P4501A2 细胞色素P4502E1 

分 类 号：R96[医药卫生—药理学]