Experimental evaluation of iosefamate meglumine and its derivatives as hepatobiliary CT contrast agents

Iosefamate meglumine has attracted attention as a possible hepatobiliary contrast agent for CT scanning. However, its limited hepatic opacification has prevented clinical acceptance. To find a more efficient agent, the efficacy and toxicity of six derivatives of iosefamate were compared with those of the parent compound in dogs. Twenty dogs received intravenous doses ranging from 150 to 600 mg I/kg of one of these seven water-soluble, ionic, dimeric agents. Three control animals received equivalent amounts of physiologic saline. The CT densities of liver, biliary tract, kidneys, and blood were then measured for up to 3 hr. Toxicity tests of liver and kidney function were performed for up to 3 days. Among the new agents, only MI-294, a previously unreported compound, proved to be a slightly more efficient hepatic opacifier than iosefamate (0.40 vs. 0.34 H per mg I/kg, respectively). MI-294 was also the least toxic. However, transient abnormalities in at least one liver function test were observed with every agent at some dose level. One animal died with hepatic necrosis after receiving iosefamate. No renal impairment was noted in any case. MI-294 has advantages over iosefamate as a CT liver and biliary opacifier in dogs. Potential hepatotoxicity of this class of agents needs to be more fully evaluated.