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Xenobiotica
the fate of foreign compounds in biological systems
Volume 51, 2021 - Issue 1
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General Xenobiochemistry

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

, , , , , & show all
Pages 51-60 | Received 09 Jun 2020, Accepted 07 Aug 2020, Published online: 25 Aug 2020
 

Abstract

  1. 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.

  2. 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.

  3. 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.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

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