SPECIES AND SEX VARIATION IN THE HEPATIC METABOLISM OF H³-DIGOXIN IN VITRO

¹ Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

The in vitro metabolism of H³-digoxin was studied for a variety of experimental variables. Nine to 11 different metabolic fractions were quantitatively isolated by liquid extraction followed by column and paper chromatography. The optimum pH for rat liver slices to metabolize H3-digoxin was found to be approximately pH 7.4. The metabolism was studied with liver slices from adult male dogs, cats, rats, mice, rabbits and guinea pigs. The rabbit slices produced the greatest amount of metabolism with only 30% remaining unmetabolized after 5 hr. The largest increases in metabolites for rabbits were found to be bisdigitoxoside and the alcohol-soluble fraction. Dog and guinea-pig slices produced increases in the aqueous alcohol-soluble fractions, whereas the dog, cat and guinea-pig produced decreases in the digoxigenin fraction. The rat and guinea pig had increases in the bisdigitoxoside fraction, whereas the mouse did not produce significant changes for any of the metabolic fractions. Both male and female rat liver slices produced significant increases for several of the metabolic fractions. The male rat produced significantly larger values for the mono and bisdigitoxosides than did the female rat. Metabolism of H³-digoxin was also studied in rabbit liver slices from both sexes at various time intervals. The decrease in digoxin was found to be approximately linear over the 5-hr period with little differences between the two sexes. The ability of rabbit homogenates to metabolize digoxin was also studied and these homogenates were found to be much less efficient than rabbit liver slices.