Diatrizoate contrast agents: 2-amino-5-acetamido-, and 3,5-diamino-2,4,6-triiodobenzoates

We have examined the metabolic behavior of several triiodobenzoic acid derivatives because of the observed mutagenicity and cytotoxicity of 3-amino-5-acetamido-2,4,6-triiodobenzoate (I) and 3,5-diamino-2,4,6-triiodobenzoate (II). Measurements were facilitated using iodine-131 (131I)-labeled compounds. Drug retention in rabbits was monitored with a gamma camera. Metabolic products were studied by column and thin-layer chromatography. 3,5-Diacetamido-2,4,6-triiodobenzoate (diatrizoate) was partially deacetylated by liver microsomes to I and II. II was transformed in part to another substance whose structure remains undetermined. About 1% of nominal doses of I, II, and diatrizoate were retained for several days following intracardiac injection in rabbits. The rabbit did not appreciably acetylate I to diatrizoate and converted some of II to a urinary metabolite which was similar to that formed by liver microsomes. I was present in human urine following excretory urography with diatrizoate, but II was not detected. Manufacturers of diatrizoate should further reduce the level of free aromatic amines in preparations of diatrizoate. A method of doing so is reported.