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A new zwitterionic iodinated molecule, 2-[3-(N-ethyl-2-hydroxyethyl) amino-acetamido-2, 4, 6-triiodobenzyl]-butyric acid (RCK-136) was synthesized, and its potential as an oral cholecystopaque was tested. In rats, 15 minutes following intravenous injection, RCK-136 reached maximum biliary concentration; 84% of the dose was excreted into bile. Biliary excretion of RCK-136 elicited a strong choleresis (44 ml of bile flow per mmol compound). Intravenous LD50 in rats averaged 390 mgI/kg. ED50 in rats, intradiencephalic, averaged 1.98 mgI/kg. The average densities of cholecystograms produced in three dogs with iosumetic acid and/or RCK-136 were comparable.

The biliary and urinary excretion of sodium tyropanoate (Bilopaque) and sodium ipodate (Oragrafin) were studied in unanesthetized bile-fistula dogs using stepwise, increasing, intravenous infusions of the contrast materials. A constant intravenous infusion of sodium taurocholate was administered at the rate of either 0.5 or 2.0 mu moles per min per kg throughout each experiment. The biliary excretion of sodium tyropanoate or sodium ipodate was not effected by the rate of sodium taurocholate infusion. The maximum rate of biliary excretion of sodium ipodate was significantly greater than that of sodium tyropanoate with the low taurocholate infusion, but there was no significant difference between the two with the high taurocholate infusion. With the low taurocholate infusion the maximum biliary excretion rate of sodium tyropanoate (0.956 mu moles per min per kg) and sodium ipodate (1.472 mu moles per min per kg) were significantly greater than the maximum biliary excretion of iopanoic acid (Telepaque) (0.671 mu moles per min per kg). With the high taurocholate infusion the maximum biliary excretion rates of the three contrast agents were not statistically different. Both sodium tyropanoate and sodium ipodate produced an increase in canalicular bile flow (8-11 ml per millimole). These data suggest that in clinical cholecystography sodium tyropanoate and sodium ipodate are not excreted in bile more rapidly than iopanoic acid, except when the rate of biliary excretion of bile salts is low; that is, except in patients who are fasting or those who are on a fat-free diet.

The biliary excretion of two oral cholecystographic contrast agents, iocetamic acid and iopanoic acid, were compared during low and high taurocholate infusion rates. The pharmacokinetics of these compounds after intravenous infusion were studied in bile-fistula dogs using both indirect and direct pharmacokinetic techniques. The indirect multiple infusion technique, corrected for urinary excretion, provides a reliable estimate of the maximum biliary excretion rates of either contrast agent without necessitating the sampling of biliary output. The results indicate that taurocholate facilitates the biliary excretion of both agents. At both taurocholate infusion rates studied, the maximum biliary excretion rate of iocetamic acid is greater than that of iopanoic acid.