Abstract

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

2. As different profiles of plasma protein binding (PPB) profiles were observed between PXB and humanized TK-NOG mice, f _up 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 f _up in PXB mice (38/39 compounds within a 3-fold). Thus, this artificial PXB mouse plasma could be used to evaluate PPB.

摘要

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。所述˚F _向上在PXB小鼠34/39化合物（87.2％）是人类的内3倍˚F _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; 所述˚F _向上人的人源化TK-NOG小鼠15/24化合物（62.5％）是在3倍˚F _向上。

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 _了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. 人类和SCID小鼠血浆（85:15）的混合等离子体中未结合的部分以及被与相关˚F _了在PXB小鼠（一内38/39化合物3倍）。因此，这种人工PXB小鼠血浆可用于评估PPB。