View article

1. We used chimeric mice (PXB mice®), which were repopulated with human hepatocytes, to evaluate their predictabilities of human pharmacokinetics.

2. The relationships of total clearance (CL_t) and the volume of distribution at steady state (Vd_ss) between that predicted from single-species allometric scaling (SSS) of PXB mice and the observed human values indicated good correlations for various drugs metabolized by cytochrome P450s (CYPs) and non-CYPs.

3. We examined the Dedrick plot with which the plasma concentration–time curves can exhibit superimposability using SSS of PXB mice for CL_t and Vd_ss. The predicted plasma concentration–time curves using the complex Dedrick plot from PXB mice were generally superimposed with the observed human data.

4. However, the predicted curve of diazepam was not superimposable with the observed profile. Residual mouse hepatocytes in the livers of …