Clemizole (25 mg/kg by mouth) was administered to eight control NOG mice (C1-8) and eight TK-NOG mice with humanized livers (Hu m1-8).
The relative amounts of six metabolites and clemizole in plasma 30 minutes after administration were measured. This table shows the human serum albumin (hAlb) concentration (mg/ml) in the humanized liver mice expressing a TK-NOG and the relative abundances of clemizole metabolites in plasma. The ratio indicates the average amount of each metabolite in humanized TK-NOG mice divided by that in control mice. Although both groups had equivalent relative amounts of three metabolites (P >0.3), the humanized mice had a significantly increased relative amount of the M1 and M6 metabolites and a significantly decreased relative amount of M14.
| Variable | hAlb | Clem | M1 | M2 | M6 | M12 | M14 | M15 |
|---|---|---|---|---|---|---|---|---|
| C1 | 4.1 | 4.1 | 10.4 | 14.1 | 28.3 | 37.5 | 1.4 | |
| C2 | 5.5 | 3.2 | 8.1 | 12.9 | 37.9 | 31.2 | 1.2 | |
| C3 | 6.8 | 2.3 | 3.3 | 8 | 24 | 50.6 | 4.8 | |
| C4 | 3.1 | 3.1 | 8 | 9.3 | 20.5 | 39.3 | 16.7 | |
| C5 | 2.8 | 8 | 5.7 | 12.1 | 27.5 | 33.3 | 10.7 | |
| C6 | 6.03 | 5.49 | 20.00 | 10.19 | 28.78 | 28.50 | 1.01 | |
| C7 | 3.81 | 1.79 | 6.52 | 12.17 | 27.04 | 47.22 | 1.46 | |
| C8 | 4.53 | 6.43 | 11.38 | 10.17 | 25.76 | 40.71 | 1.02 | |
| Hu m1 | 4.2 | 1.8 | 8.9 | 13.6 | 8.3 | 20.6 | 39.8 | 6.9 |
| Hu m2 | 1.5 | 4.4 | 7.1 | 8.3 | 13 | 29.6 | 35.5 | 2.4 |
| Hu m3 | 1.6 | 5.3 | 7.9 | 9.2 | 16.8 | 32.1 | 26.9 | 1.8 |
| Hu m4 | 2.2 | 4.3 | 7.1 | 14.2 | 5.9 | 14.8 | 48.5 | 5.2 |
| Hu m5 | 2.7 | 3.6 | 13.1 | 10 | 26 | 29 | 16.5 | 1.8 |
| Hu m6 | 1.3 | 6.25 | 12.25 | 18.24 | 23.10 | 26.37 | 12.33 | 1.46 |
| Hu m7 | 7 | 8.75 | 10.73 | 18.66 | 21.30 | 28.86 | 9.59 | 2.12 |
| Hu m8 | 1.6 | 7.02 | 9.04 | 13.59 | 19.92 | 28.77 | 20.69 | 0.97 |
| Ratio | 1.13 | 2.21 | 1.44 | 1.51 | 0.96 | 0.68 | 0.59 | |
| P value | 0.526 | 0.0004 | 0.095 | 0.049 | 0.659 | 0.046 | 0.389 |