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

Characterization of plasma protein binding in two mouse models of humanized liver, PXB mouse and humanized TK-NOG mouse. Xenobiotica. 2020 Aug 11;:1-46 Authors: Miyamoto M, Kosugi Y, Iwasaki S, Chisaki I, Nakagawa S, Amano N, Hirabayashi H Abstract 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.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.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. PMID: 32779988 [PubMed - as supplied by publisher]
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research