Bioavailability of drugs: the digoxin dilemma

The absorption of oral digoxin preparations has been a topic of much concern during the last 5 years. The completeness of digoxin absorption is proportional to the area under the serum concentration time curve and to the urinary excretion of digoxin after single doses. During chronic therapy the completeness of absorption is proportional to these values and also to the steady state serum concentration. Determination of absolute bioavailability of a given digoxin preparation requires a comparative study using intravenous digoxin as a standard. Oral digoxin solutions are incompletely absorbed, but have biological availability greater than or equal to that of tablets. The absorption of digoxin tablets depends upon their dissolution rate which in turn is related to drug particle size. Digoxin tablets with small drug particles have rapid rates of dissolution and can be absorbed as completely as oral solutions. The bioavailability of digoxin from tablets can be influenced by changes in gastro-intestinal motility, malabsorption syndromes, and by co-administration of food or other drugs. New regulations now insure that all marketed digoxin tablet preparations have satisfactory bioavailability. Problems with biological availability at present are unlikely to account for unexpected clinical results during digoxin therapy.