Predictability of human exposure by human-CYP3A4-transgenic mouse models: A meta-analysis.

ABSTRACT: First-in-human dose predictions are primarily based on no-observed-adverse-effect levels in animal studies. Predictions from these animal models are only as effective as their ability to predict human results. To narrow the gap between human and animals, researchers have, among other things, focused on the replacement of animal cytochrome P450 (CYP) enzymes with their human counterparts (called humanization), especially in mice. Whereas research in humanized mice is extensive, the emphasis has been particularly on qualitative rather than quantitative predictions. Because the CYP3A4 enzyme is most involved in the metabolism of clinically used drugs, most benefit was expected from CYP3A4 models. There are several applications of these mouse models regarding in vivo CYP3A4 functionality, one

SUBMITTER: Damoiseaux D 

PROVIDER: S-EPMC10766057 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature