期刊文献+

体内代谢法研究新药对细胞色素P450 1A2和2E1的影响 被引量:9

Effects of new drun metabolism on CYP1A2 and CYP2E1
下载PDF
导出
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.
出处 《肝脏》 2008年第5期387-389,417,共4页 Chinese Hepatology
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 New drug Safety Caffeine Chlorzoxazone CYP1A2 CYP2E1
  • 相关文献

参考文献9

  • 1王晓今,陈成伟,刘光华,傅青春,倪鎏达,赖荣陶,齐慧慧,陈姝.231例药物性肝损伤临床分析[J].肝脏,2007,12(5):363-365. 被引量:15
  • 2陈成伟.药物性肝病的发病机制及诊治[J].肝脏,2007,12(4):297-302. 被引量:53
  • 3Frye RF, Matzke GR, Adedoyin A, et al. Validation of the fivedrug " Pittsburgh cocktail" approach for assensement of selective regulation of drug metabolizing enzymes. Clin Pharmacol Ther, 1997,62 : 365-376.
  • 4Streetrnan DS, Bleakley JF, Kim JS, et al. Combined phenotypic assessment of CYP1A2, CYP2C19, CYP2D6, CYP3A, N-acetyL-transferase 2,and xanthine oxidase with the " Cooperstown cocktail". Clin Pharmacol Ther, 2000,68 :375-383.
  • 5Tucker GT, Houston JB, Huang SM. Optimizing drug develop ment:strategies to assess drug metabolism/transporter interaction potential toward a consensus. Pharm Res, 2001,18 : 1 071-1080.
  • 6马璟,钱蓓丽.人类细胞色素P450s研究概况及其在新药安全性评价中的应用[J].中国新药杂志,2002,11(1):36-42. 被引量:22
  • 7Vieira IM, Sonnier M, Cresteil T. Developmental expression of CYP2E1 in the human liver. Hypermethylation control of gene expression during the neonatal period. Eur J Bioehem, 1996,238 : 476- 483.
  • 8Hickman D,Wang JP,Wang Y,et al. Evaluation of the selectivity of in vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metab Dispos, 1998, 26:207-215.
  • 9Kharasch ED, Thummel KE, Mhyre J, et al. Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1. Clin Pharmacol Ther,1993,53:643- 650.

二级参考文献16

  • 1舒炎 王永铭 等.细胞色素P450药物氧化代谢酶的遗传药理学进展.药理学进展[M].北京:科学出版社,2000.19-31.
  • 2周宏灏.分子遗传药理学.分子药理学[M].哈尔滨:黑龙江科学技术出版社,1999.224-251.
  • 3陈成伟.药物性肝病的发病机制及诊治[J].肝脏,2007,12(4):297-302. 被引量:53
  • 4陈成伟.细胞色素P450遗传多态性意义及其基因型与表型的检测[A].见:陈成伟 主编.药物与中毒性肝病 第1版[C].上海:上海科学技术出版社,2002.312-327.
  • 5陈成伟,姜丽静.草药和植物的肝脏毒性.见:姚光弼,主编.临床肝脏病学.上海:上海科学技术出版社,2004.528-537.
  • 6Lee WM.Drug-induced hepatotoxicity.N Engl J Med,2003,349:474-485.
  • 7Lee WM.Acetaminophen and the U.S.acute liver failure study group:lowering the risks of hepatic failure.Hepatology,2004,40:6-9.
  • 8Evans DC,Watt AP,Nicoll-Grifith DA,Baillie TA.Drug-protein adducts:an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development.Chem Res Toxicol,2004,17:3-16.
  • 9Park BK,Kitteringham NR,Maggs JL,Pirmohamed M,Williams RP.The role of metabolic activation in drug-induced hepatotoxicity.Annu Rev Pharmacol Toxicol,2005,45:177-202.
  • 10Pelli N,Setti M,Ceppa P,et al.Autoimmune hepatitis revealed by atorvastatin.Eur J Gastroenterol Hepatol,2003,15:921-924.

共引文献86

同被引文献108

引证文献9

二级引证文献54

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部