Additive renal effects of indomethacin and dipyridamole in man

The effect of dipyridamole alone and in combination with indomethacin was studied in 11 water loaded rheumatic patients with normal kidney function. The adenosine uptake inhibitor dipyridamole and the prostaglandin synthesis inhibitor indomethacin decreased diuresis by 25-50% when given alone and by approximately 80% when combined. These effects were not associated with changes in renal PAH-clearance, but may be partially related to a fall in GFR. Sodium excretion was decreased in parallel with the fall in GFR. In addition, both indomethacin and dipyridamole reduced the free water clearance. Theophylline at therapeutic plasma levels reversed the reduction in GFR and transiently counteracted the inhibition of tubular water and sodium excretion induced by combined dipyridamole and indomethacin treatment. The results suggest that endogenous adenosine and prostaglandins are both involved in the control of renal function in man, and that drugs that affect these two autocoids may interact to cause adverse effects in man.