EXCRETION AND DISTRIBUTION OF IOPHENOXIC ACID

¹ Departments of Medicine and of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

The cholecystographic agent, iophenoxic acid (Teridax), has a plasma half-life of at least 2 years. The mechanisms have not been previously examined. In experiments in 12 dogs, measurements were made of biliary and urinary clearance, plasma binding, tissue distribution, chronic balances and several aspects of renal excretion, including stop-flow. The dog appears to be an appropriate model in which to study persistence. Administration of ¹²⁵I-labeled compound resulted in prompt initial excretion of conjugates in bile and urine, followed by very low rates when plasma level declined to the 50 to 100 µg/ml range. There was strong plasma binding, but no evidence for unusual tissue sequestration. Biliary clearance (range 0.005 to 12 ml/min/10 kg) usually exceeded urinary (range 0.004 to 4 ml/min/lO kg). At low plasma levels, the amount excreted in the bile largely underwent intestinal reabsorption. Under some conditions, renal tubular secretion was demonstrated (probably conjugates), but net tubular reabsorption was usually dominant. Alkiilinisation of urine or forced diuresis had little effect on renal excretion. Hepatic conjugation (estimated as sum of biliary plus urinary excretion) was extremely sensitive to plasma concentration, so that at 50 µg/ml a 2-fold change in plasma level was associated with a 100-fold or greater change in conjugation rate. This relationship probably underlies unique persistence.