H³-DIGOXIN METABOLISM BY ADULT MALE RAT TISSUES IN VITRO

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

Certain conditions for the in vitro metabolism of H⁸-digoxin were investigated in the rat. Liver homogenates did not metabolize the drug. Up to 20% of initial radioactivity was recovered as metabolites after incubations of liver slices. Metabolism of H³-digoxin resulted in formation of digoxigenin-bisdigitoxoside, digoxigenin-monodigitoxoside, digitoxose, and a decrease in recoverable digoxigenin. Other possible metabolites have not yet been identified.

Metabolism increased with time, and four times as much bisdigitoxoside was recovered after 5 hours as after 1 hour. A decrease in the amount of digoxigenin was also found after 5 hours. Incubations under nitrogen resulted in no significant metabolism. Metabolism was noted with only sodium chloride and potassium chloride added as constituents to the pH 7.4 phosphate buffer.

Liver slices were the only tissue preparations tested that resulted in any significant metabolism. No significant metabolism was noted when heart, kidney or adrenal slices were studied.