TABLE 2

Disposition pattern for the three major metabolites of furosemide

Furosemide is metabolized into three different metabolites in mice (Williams et al., 2007): 1) a dealkylated metabolite (dealkylated-FS); 2) a glucuronide (FS-glucuronide); and 3) a ketocarboxylic acid metabolite, which can also be conjugated with glutathione (glutathione-FS). Their amounts in urine and feces obtained from control and humanized male TK-NOG mice (n = 4 mice per group) were measured over a 24-hour period after administration of furosemide (200 mg/kg i.p.). The liver samples were obtained 24 hours after furosemide dosing. Each data point represents the average of the relative abundance of the indicated metabolite in each of the collected materials obtained from control or humanized mice. P values for the difference between the values obtained for control and humanized TK-NOG mice are also shown.

LiverFecesUrine
Dealkylated-FSControl7.021.8254.40
Humanized2.494.6034.13
Ratio2.80.41.6
P value0.0320.1710.024
Ketocarboxylic acidControl1.500.02100.82
Humanzicd0.030.5738.34
Ratio47.30.042.6
P value0.0280.3240.028
Glucuronide-FS totalControl9.260.03206.11
Humanized2.3413.07249.17
Ratio4.00.0030.8
P value0.2910.3280.681
FS-glutathioneAll below the level of detection