Characterization of plasma protein binding in two mouse models of humanized liver, PXB mouse and humanized TK-NOG mouse
Creators: name: Miyamoto, Maki
name: Kosugi, Yohei
name: Iwasaki, Shinji
name: Chisaki, Ikumi
name: Nakagawa, Sayaka
name: Amano, Nobuyuki
name: Hirabayashi, Hideki
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Neuroscience
subject: Physiology
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: Hematology

description: The unbound fractions in plasma (<i>f</i><sub>up</sub>) in two mouse models of humanized liver mice, PXB and humanized TK-NOG mice, were compared with human <i>f</i><sub>up</sub> values using equilibrium dialysis method. A good relationship between <i>f</i><sub>up</sub> values obtained from PXB mice and humans was observed; the <i>f</i><sub>up</sub> of 34/39 compounds (87.2%) in PXB mice were within 3-fold of human <i>f</i><sub>up</sub>. In contrast, a weak correlation was observed between human and humanized TK-NOG mouse <i>f</i><sub>up</sub> values; the <i>f</i><sub>up</sub> of 15/24 compounds (62.5%) in humanized TK-NOG mice were within 3-fold of human <i>f</i><sub>up</sub>.As different profiles of plasma protein binding (PPB) profiles were observed between PXB and humanized TK-NOG mice, <i>f</i><sub>up</sub> 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 <i>f</i><sub>up</sub> in PXB mice (38/39 compounds within a 3-fold). Thus, this artificial PXB mouse plasma could be used to evaluate PPB. The unbound fractions in plasma (<i>f</i><sub>up</sub>) in two mouse models of humanized liver mice, PXB and humanized TK-NOG mice, were compared with human <i>f</i><sub>up</sub> values using equilibrium dialysis method. A good relationship between <i>f</i><sub>up</sub> values obtained from PXB mice and humans was observed; the <i>f</i><sub>up</sub> of 34/39 compounds (87.2%) in PXB mice were within 3-fold of human <i>f</i><sub>up</sub>. In contrast, a weak correlation was observed between human and humanized TK-NOG mouse <i>f</i><sub>up</sub> values; the <i>f</i><sub>up</sub> of 15/24 compounds (62.5%) in humanized TK-NOG mice were within 3-fold of human <i>f</i><sub>up</sub>. As different profiles of plasma protein binding (PPB) profiles were observed between PXB and humanized TK-NOG mice, <i>f</i><sub>up</sub> 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 <i>f</i><sub>up</sub> in PXB mice (38/39 compounds within a 3-fold). Thus, this artificial PXB mouse plasma could be used to evaluate PPB.