Digitoxin metabolism by rat, mouse, and rabbit: NADPH requirement and spironolactone effect.

Digitoxin metabolism in rat, mouse, and rabbit liver homogenates was compared. The rabbit metabolized the compound most extensively, yielding digitoxigenin as major hydrolysis product. Rat and mouse both produced digitoxigenin bisdigitoxoside as major product. Metabolite formation was enhanced by NADPH in all three species. Spironolactone induced the hydrolysis of digitoxin in the rat, but had no effect in the mouse or rabbit. The mechanism of the protective effect of spironolactone in the mouse does not involve induction of digitoxin hydrolysis; in the rabbit, rapid inactivation of spironolactone accounts for the lack of induction.