Tienilic Acid: Pharmacokinetics, Salicylate Interaction and Creatinine Secretion Studies

Tienilic acid is a diuretic-uricosuric compound whose natriuretic site of action is in the cortical diluting segment of the distal nephron. Oral doses of 250 mg given to normal human volunteers provided peak blood levels of 10--11 micrograms/ml at 3--4 hours after administration. Approximately 40% of the dose was recovered in 24 hours, 30% as the parent compound and 10% as the alcohol and diacid metabolites. A 650 mg dose of acetylsalicylic acid significantly decreased the uricosuric effect of tienilic acid by inhibiting uric acid secretion. Urine pH fell significantly with tienilic acid administration. Tienilic acid inhibited salicylate excretion by either competition for tubular secretion or by increasing passive, pH dependent reabsorption. In normal subjects given a creatinine load, tienilic acid did not inhibit creatinine secretion.