Dipyridamole inhibition of adenosine metabolism in human blood.

The effects of dipyridamole on the metabolism of adenosine were studied in human whole blood. The half-life for adenosine disappearance and the formation of deamination and phosphorylation products were determined by adding [3H]adenosine to blood incubating at 37 degrees C. The initial adenosine concentration was 10 nmol/ml blood. Aliquots of blood were removed at specific times following the addition of labelled adenosine. The aliquots were later assayed for adenosine and its products by reverse-phase high pressure liquid chromatography. The half-life for adenosine in undiluted blood was less than 10 s; therefore, to accurately evaluate the effects of dipyridamole, blood was diluted 1 : 12 in isotonic saline. At this dilution, the half-life for adenosine was 1.3 min. Dipyridamole concentrations of 1 nmol/ml blood caused 90% inhibition of adenosine metabolism. Inhibition was virtually complete, except for plasma deamination, at concentrations greater than 10 nmol/ml blood. Since these inhibitory concentrations of dipyridamole are on the same order as those achieved therapeutically in man, these data indicate that dipyridamole at therapeutic concentrations causes significant inhibition of adenosine metabolism in whole blood.