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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
Quelle
MEDLINE
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.