Renal excretion of an angiotensin I converting enzyme inhibitor (SA-446) in dogs.

The renal excretory mechanism of an orally active inhibitor of angiotensin converting enzyme (SA-446) was examined in anesthetized dogs. Parenteral administration of this compound resulted in production of constant levels of about 2 mg/l in the plasma (PSA) and the urine concentration was 726 +/- 200 mg/l, a level significantly higher than that in the plasma. Renal clearance of SA-446 (CSA) was 2.24 +/- 0.34 ml/g X min and was significantly higher than GFR. The clearance ratio (CSA/GFR) of over 1.0 was indicative of a net tubular secretion. Administration of probenecid resulted in a significant rise in PSA and in a significant decrease in urinary excretion but with no change in the plasma protein binding ratio. CSA decreased significantly from 2.24 +/- 0.34 to 0.71 +/- 0.14 ml/g X min. The inhibitory action of SA-446 (0.02 mg/kg, i.v.) on the pressor response to angiotensin I disappeared at about 50 min, this action being maintained for about 2 h in the probenecid pretreated dog. Since probenecid is a competitive inhibitor of organic anion secretory transport, our results show the net tubular secretion of SA-446, via organic anion transport systems. Prolongation of the action of SA-446, as induced by probenecid may be due to the increase of plasma concentration, by the inhibition of tubular secretion.