TABLE 1

Characterization of metabolic activity (phase I and phase II metabolism of 7-ethoxycoumarin) in human, rat, monkey, and mouse precision-cut liver slices

Liver slices were incubated with 50 μM 7-ethoxycoumarin for 3 h at 37°C. Values represent means ± S.E.M. of three replicate incubations.



Metabolite Formation

7-HC
7-HC-O-sulfate
7-HC-O-glucuronide
Total
nmol/g liver
Human donors
045-22445 33.7 ± 2.4 69.8 ± 7.0 90.1 ± 6.1 193.6 ± 15.3
045-23079 38.7 ± 2.0 62.4 ± 1.7 75.8 ± 5.2 177.0 ± 7.5
Fischer 344 rat 21.7 ± 1.6 372.7 ± 14.1 64.2 ± 4.7 458.7 ± 19.6
Cynomolgus monkey 181.1 ± 20.1 1,792.6 ± 28.7 706.4 ± 31.3 2,680.0 ± 30.6
Rhesus monkey 89.2 ± 5.1 1,014.8 ± 48.5 656.5 ± 56.3 1,760.5 ± 101.5
CD-1 mouse
91.5 ± 7.4
679.9 ± 176.0
1,105.0 ± 351.0
1,876.5 ± 530.5
  • 7-HC, 7-hydroxycoumarin.