Pharmacokinetics and Mode of Action of Tienilic Acid

A review of the absorption, distribution, metabolism and excretion of ticrynafen (tienilic acid) in 8 animal species, including man, is presented. Although some species effects are apparent, ticrynafen absorption is essentially complete following oral administration. The compound is extensively bound to plasma proteins, primarily albumin. Consequently, tissue concentrations are generally lower than plasma concentrations. Plasma and whole body clearance of ticrynafen is rapid due both to metabolism and to extensive renal excretion of the compound and its metabolites. Male/female differences in renal excretion occur, with a subsequent effect on ticrynafen metabolism.Ticrynafen is an inhibitor of reabsorption of sodium and uric acid by the kidney. This inhibitory effect, within the renal tubular lumen, accounts for its diuretic and uricosuric activity and could account for its antihypertensive activity, although a direct effect has also been claimed.Ticrynafen is also a classical example of a competitive inh...