Details

Autor(en) / Beteiligte

• Miyamoto, Maki
• Kosugi, Yohei
• Iwasaki, Shinji
• Chisaki, Ikumi
• Nakagawa, Sayaka
• Amano, Nobuyuki
• Hirabayashi, Hideki

Titel

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

Ist Teil von

• Xenobiotica, 2021-01, Vol.51 (1), p.51-60

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2021

Link zum Volltext

Beschreibungen/Notizen

• 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 (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.