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Therapeutic and toxic actions of cardiac glycosides are attributed to an inhibition of Na, K-ATPase. The therapeutically relevant range is between 25% and 50% inhibition. There is a good correlation between the average steady state serum concentration of glycosides and their therapeutic action. However, therapeutic and toxic effects set in with a latency and therefore do not follow the daily variations in glycoside concentration. Although the effect follows the average serum concentrations, only the minimal concentration is measured. In principle this is only adequate if the ratio of average/minimal concentration is constant. A model calculation showed that with a constant average steady state concentration an increase in the distribution volume or a decrease in total body clearance with corresponding reduction of the daily dose lead to an increase of the minimal concentrations of 5-7%. This means a corresponding underestimation of the average concentration from the minimum concentration. However, the deviations are too small to be of clinical relevance.

Tritiated ouabain, digitoxin, and digoxin were given IV to anesthetized guinea pigs. The tritium content of the ocular tissues (cornea, iris, lens, vitreous body, retina, choroid, sclera, and optic nerve) was measured after 1 and 3 h and compared with the amount of tritium found in the brain and some peripheral organs. High levels of digitoxin were found in the brain and retina. Digoxin was detected in large quantities in the retina, but only small levels were found in brain tissue. Ouabain was nearly absent in the retina and cerebrum, whereas in most other ocular and peripheral tissues the three cardiac glycosides were present in comparable quantities. The IP injection of tritiated digoxin resulted in lower absolute tissue levels, but a pattern of distribution similar to that observed in anesthetized guinea pigs was found in conscious animals.