Characterization of plasma protein binding in two mouse models of humanized liver, PXB mouse and humanized TK-NOG mouse.
Xenobiotica
; 51(1): 51-60, 2021 Jan.
Article
en En
| MEDLINE
| ID: mdl-32779988
ABSTRACT
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. 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. The unbound fraction in the mixed plasma of human and SCID mouse plasma (8515) 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Xenobiotica
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón