Characterization of plasma protein binding in two mouse models of humanized liver, PXB mouse and humanized TK-NOG mouse

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.

Keywords:

• Albumin
• alpha-1 acid glycoprotein
• chimeric humanized mouse
• plasma protein binding
• PXB mouse
• TK-NOG mouse
• unbound fraction

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This article has been republished with minor changes. These changes do not impact the academic content of the article.

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