In vivo drug interactions of the teratogen thalidomide with midazolam: heterotropic cooperativity of human cytochrome P450 in humanized TK-NOG mice.
In vivo drug interactions of the teratogen thalidomide with midazolam: heterotropic cooperativity of human cytochrome P450 in humanized TK-NOG mice.
复制标题
DOI：
10.1021/tx400008g
复制
发表时间：
2013-03-18
影响因子：
4.1
通讯作者：
Guengerich FP
中科院分区：
文献类型：
--
作者：
Yamazaki H;Suemizu H;Murayama N;Utoh M;Shibata N;Nakamura M;Guengerich FP
在人源化肝脏小鼠中研究了致畸原沙利度胺与模型细胞色素P450 (P450) 3A底物咪达唑仑的体内药物相互作用。同时口服沙利度胺（100 mg kg - 1）可增强咪达唑仑（静脉注射，10 mg kg - 1）对嵌合小鼠的清除率。由于人类P450 3A酶的异向协同作用，与沙利度胺的主要代谢物1′-羟咪唑仑的曲线下面积较高（1.7倍）。每日使用沙利度胺预处理3天，可观察到轻微代谢物4-羟咪唑仑曲线下面积较高（3.5倍），可能是由于人P450 3A诱导所致。这些结果表明，人源化小鼠的肝脏介导了沙利度胺的药物相互作用，并提示治疗药物在沙利度胺治疗期间的相互作用。
In vivo drug interactions of the teratogen thalidomide with the model cytochrome P450 (P450) 3A substrate midazolam were investigated in mice with humanized livers. The clearance of midazolam (administered intravenously, 10 mg kg−1) in chimeric mice was enhanced by orally co-administered thalidomide (100 mg kg−1). A higher area-under-the-curve of the major metabolite 1′-hydroxymidazolam (1.7-fold) was obtained with thalidomide due to heterotropic cooperativity of human P450 3A enzymes. A higher area-under-the-curve of the minor metabolite 4-hydroxymidazolam (3.5-fold) was seen by pre-treatment with thalidomide daily for 3 days, presumably because of human P450 3A induction. These results demonstrate that livers of humanized mice mediate drug interactions of thalidomide and suggest interactions of therapeutic agents during therapies with thalidomide.
登录
查看更多内容
影响因子：
2.3
作者：
Rendic S;Guengerich FP
通讯作者：
Guengerich FP
影响因子：
3.8
作者：
Kim, James H.;Scialli, Anthony R.
通讯作者：
Scialli, Anthony R.
影响因子：
4.1
作者：
Chowdhury, Goutam;Murayama, Norie;Yamazaki, Hiroshi
通讯作者：
Yamazaki, Hiroshi
影响因子：
3.3
作者：
Eriksson, T;Björkman, S;Höglund, P
通讯作者：
Höglund, P
影响因子：
4.1
作者：
Yamazaki H;Suemizu H;Shimizu M;Igaya S;Shibata N;Nakamura M;Chowdhury G;Guengerich FP
通讯作者：
Guengerich FP