THE ABSORPTION, DISTRIBUTION AND EXCRETION OF K-STROPHANTHOSIDE-³H IN GUINEA PIGS AFTER PARENTERAL ADMINISTRATION

¹ Biochemistry and Haemodynamic Division, Istituto Simes di Cardiologia Sperimentale and Institute of Biological Chemistry, State University, Milan, Italy

Isolated guinea-pig hearts perfused 64 minutes with K-strophanthoside-³H according to Dutta showed a specific uptake in the ventricles that was higher than in the atria. The supernatant/pellet ratio of the drug in heart homogenates was 0.5. The highest specific concentration of K-strophanthoside among particulate fractions was in the microsome fraction. In anesthetized guinea pigs with a biliary fistula K-strophanthoside showed an intestinal absorption that was virtually the same as that of ouabain, but a biliary excretion and enterohepatic circulation about 6 times higher than ouabain. Both K-strophanthoside and ouabain excreted in bile and urine and that present in the small intestine contents were recovered as such. The pharmacokinetic parameters of K-strophanthoside-³H administered intravenously and intramuscularly to conscious guinea pigs at a myocardial active dose of 250 µg/kg were studied. The animals were sacrificed in groups of 7 after 15 and 30 minutes, 1, 2, 5, 10 and 24 hours. With both i.v. and i.m. routes, the highest levels of K-strophanthoside-³H were found in the urine; bile and intestine contents showed the next highest levels; high levels were also found initially in the kidneys, liver and heart, but they decreased with time. Levels in other organs, tissues and fluids were lower. The highest cumulative amount of the drug present in the body (except intestine contents and urine) was 93% 15 minutes after the i.v. route and 77% 1 hour after time i.m. route. After 24 hours these amounts were about 31% for both i.v. and i.m. routes. Urinary excretion of the drug and the amount present in the intestine contents arising from biliary excretion were both almost the same after 24 hours, ranging from 30 to 40%. K-strophanthoside present in the bile and urine was recovered unchanged.