采用肝微粒体研究夫拉平度葡萄糖醛酸化代谢的性别及种属差异  

Glucuronidation of Flavopiridol by Liver Microsomes in Vitro:A Species and Gender Comparison

作　　者：柳茜[1] 谢利霞[2] 石剑[1] 刘中秋[1] 夏笔军[1] 

机构地区：[1]南方医科大学药学院,广州510515 [2]深圳市南山区人民医院药剂科,广东深圳518052

出　　处：《中国药学杂志》2012年第13期1048-1051,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30873321)

摘　　要：目的研究夫拉平度(flavopiridol)在不同种属不同性别肝微粒体中葡萄糖醛酸化(UDP-glucuronosyl transferase,UGT)代谢速率及代谢机制。方法采用人和4种动物(小鼠、大鼠、豚鼠、狗)雌雄两种性别的肝微粒体酶对夫拉平度的酶代动力学进行研究,以超高效液相色谱法测定葡萄糖醛酸化代谢反应物的浓度,比较葡萄糖醛酸化代谢速率。结果夫拉平度在各种肝微粒体中都能被代谢并生成葡萄糖醛酸结合物。同一性别的5种动物的肝微粒体代谢夫拉平度的速率有种属差异(P<0.05),狗、豚鼠肝微粒体中夫拉平度的葡萄糖醛酸化代谢速率存在性别差异(P<0.05),人、大鼠、小鼠性别差异不明显。结论夫拉平度在各种肝微粒体中的代谢途径主要是葡萄糖醛酸化代谢反应,夫拉平度在人肝微粒体中葡萄糖醛酸化代谢速率性别差异不明显,但存在明显的种属差异。OBJECTIVE To study the species-dependent and gender-dependent glucuronidation of flavopiridol by human liver microsomes for providing some useful information to clinical application. METHODS Ten kinds of liver microsomal （ male mouse, rat, guinea pig, dog, human and female mouse, rat, guinea pig, dog, human） incubation systems were used to investigate the UGT （UDP-glucuronosyl transferase） metabolism. The amounts of flavopiridol glucuronides in samples were determined by ultra performance liquid chromatography （UPLC）. RESULTS Flavopiridol was metabolized to flavopiridol glucuronide in each selected kind of micro- somes. Species-dependent glucuronidation rates of flavopiridol displayed significant differences in the same gender （ P 〈 0. 05 ）. Signif- icant difference was observed between the glucuronidation rates of dog and guinea pig （ P 〈 0. 05 ） , while not observed among those of human, rat and mouse. CONCLUSION Glucuronidation is the dominant pathway in the metabolism of flavopiridol. There was no significant difference between the glucuronidation rate in human male liver microsomes and that in human female liver microsomes, while the species-dependence was markedly observed.

关 键 词：夫拉平度 肝微粒体 性别差异 种属差异 葡萄糖醛酸化 

分 类 号：R944[医药卫生—药剂学] R969[医药卫生—药学]