Cardiac glycosides and their metabolites levels in plasma and heart of guinea-pigs after I. V. administration.

One hr, 3 hr and 6 hr after i.v. injection of tritiated gitoxin, digoxin and digitoxin to the guinea-pig, the chloroform-insoluble metabolites, mainly conjugates known to be cardio-inactive, represent two thirds of the cardiac glycoside and metabolites content of plasma for gitoxin, half for digitoxin and one quarter for digoxin. Most of the compounds taken up by the myocardium are chloroform-soluble and may be considered as cardio-active. Considering the nature and proportions of the unchanged cardiac glycoside and its cardio-active metabolites in the myocardium of the guinea-pig, the cardiac effects that would be measured after administration of digoxin ar due to unchanged digoxin only; after administration of digitoxin, these effects are partly due to unchanged digitoxin but also to 12 beta-hydroxylated metabolites; after administration of gitoxin, besides unchanged gitoxin, the hydrolysis products of the sugar chain of gitoxin may contribute to the cardiac effects. The data obtained in plasma and in myocardium between 1 and 6 hr after administration of digoxin or gitoxin show that the distribution of the unchanged cardiac glycoside and each chloroform-soluble metabolite, from plasma to myocardium, is achieved 1 hr after administration. This situation does not occur with digitoxin and its metabolites.