Table 2 AUC0-inf of metabolites after single intravenous administration of S-warfarin at 4.0 mg/kg to wild-type, POR cKO, Normal Hu-liver, and POR cKO Hu-liver mice.

From: Humanized liver TK-NOG mice with functional deletion of hepatic murine cytochrome P450s as a model for studying human drug metabolism

Metabolite

Mouse

AUC0-inf (μg h/mL)

AUC ratioa

4′-Hydroxywarfarin

Wild-type mouse A

1700

–

Wild-type mouse B

1800

–

POR cKO mouse A

3.3

0.0019

POR cKO mouse B

6.3

0.0036

Normal Hu-liver mouse A

700

0.4000

Normal Hu-liver mouse B

750

0.4300

POR cKO Hu-liver mouse A

68

0.0390

POR cKO Hu-liver mouse B

140

0.0800

6-Hydroxywarfarin

Wild-type mouse A

240

–

Wild-type mouse B

170

–

POR cKO mouse A

0.18

0.00088

POR cKO mouse B

0.28

0.00140

Normal Hu-liver mouse A

280

1.4

Normal Hu-liver mouse B

320

1.6

POR cKO Hu-liver mouse A

450

2.2

POR cKO Hu-liver mouse B

530

2.6

7-Hydroxywarfarin

Wild-type mouse A

620

–

Wild-type mouse B

530

–

POR cKO mouse A

3.3

0.0057

POR cKO mouse B

3.8

0.0066

Normal Hu-liver mouse A

1900

3.3

Normal Hu-liver mouse B

2000

3.5

POR cKO Hu-liver mouse A

2400

4.2

POR cKO Hu-liver mouse B

8700

15.0

  1. aRatios of AUC0-inf in POR cKO mice, humanized liver TK-NOG mice (Normal Hu-liver), and POR cKO humanized liver (POR cKO Hu-liver) mice compared to those in wild-type mice (mean value of two animals). Normal Hu-liver mouse A and B (human Albumin: 6.5 and 6.6 mg/mL, Cholinesterase activity 255 and 425 U/L, Replacement Index 72.5% and > 95% estimated with Cholinesterase activity), POR cKO Hu-liver mouse A and B (human Albumin: 7.6 and 8.3 mg/mL, Cholinesterase activity 265 and 470 U/L, Replacement Index 75.1% and > 95% estimated with Cholinesterase activity).
Back to article page