当前位置: X-MOL 学术Xenobiotica › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Characterization of plasma protein binding in two mouse models of humanized liver, PXB mouse and humanized TK-NOG mouse
Xenobiotica ( IF 1.3 ) Pub Date : 2020-08-11
Maki Miyamoto, Yohei Kosugi, Shinji Iwasaki, Ikumi Chisaki, Sayaka Nakagawa, Nobuyuki Amano, Hideki Hirabayashi

  1. The unbound fractions in plasma (fup) in two mouse models of humanized liver mice, PXB and humanized TK-NOG mice, were compared with human fup values using equilibrium dialysis method. A good relationship between fup values obtained from PXB mice and humans was observed; the fup of 34/39 compounds (87.2%) in PXB mice were within 3-fold of human fup. In contrast, a weak correlation was observed between human and humanized TK-NOG mouse fup values; the fup of 15/24 compounds (62.5%) in humanized TK-NOG mice were within 3-fold of human fup.

  2. As different profiles of plasma protein binding (PPB) profiles were observed between PXB and humanized TK-NOG mice, fup evaluation is necessary in each mouse model to utilize these humanized liver mice for pharmacological, drug–drug interaction (DDI), and toxicity studies.

  3. The unbound fraction in the mixed plasma of human and SCID mouse plasma (85:15) was well correlated with fup in PXB mice (38/39 compounds within a 3-fold).Thus, this artificial PXB mouse plasma could be used to evaluate PPB.



中文翻译:

人源化肝的两种小鼠模型(PXB小鼠和人源化TK-NOG小鼠)中血浆蛋白结合的特征

  1. 使用平衡透析方法,将两种人源化肝小鼠PXB和人源化TK-NOG小鼠模型中血浆的未结合部分(f up)与人f up值进行比较。观察到从PXB小鼠和人类获得的f up值之间存在良好的关系。在F向上在PXB小鼠34/39化合物(87.2%)是人F的内3倍起来。相比之下,人类之间观察到弱的相关性和人源化TK-NOG小鼠˚F向上值; 的F向上的人源化TK-NOG小鼠15/24化合物(62.5%)是人F的内3倍起来

  2. 作为血浆蛋白的不同的简档的结合物PXB和人源化TK-NOG小鼠之间观察到(PPB)型材,F向上评价是在每个小鼠模型利用药理这些人源化肝脏的小鼠,药物-药物相互作用(DDI),以及毒性必要学习。

  3. 人和SCID小鼠血浆混合血浆中的未结合部分(85:15)与PXB小鼠的f up密切相关(3倍之内有38/39种化合物),因此,这种人工PXB小鼠血浆可用于评估PPB。

更新日期:2020-08-11
down
wechat
bug