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It is well established that a number of organic anions are excreted by the liver into bile in association with a marked increase in bile flow. Previous studies have shown that iodipamide (3,3'-(adipoyl-diimino)bis[2,4,6-triiodobenzoic acid]), the radiographic contrast material used for intravenous cholangiography, is a potent choleretic. Experiments were performed in unanesthetized dogs to determine if the increased bile flow produced by iodipamide is canalicular or ductular in origin, to quantitate the choleresis associated with iodipamide and taurocholate excretion, and to correlate these findings with the results of in vitro studies in which the osmotic activities of iodipamide and taurocholate in both isotonic saline and bile were determined. The plasma erythritol clearance increase linearly with the excretion of iodipamide, indicating that iodipamide stimulates canalicular bile flow. The choleretic potency of iodipamide (22 ml/mmol) is approximately 3 times that of taurocholate (7.8 ml/mmol), yet the osmotic activity of iodipamide in bile (1.5 mosmol/mmol) is only twice as great as that of taurocholate in bile (0.8 mosmol/mmol). It therefore appears that, per unit of effective osmotic solute secreted, iodipamide carries more water into the bile canaliculi than does taurocholate.

The biliary excretion and choleretic effects of iodoxamate (Cholevue) and iodipamide (Cholografin) were compared in unanesthetized dogs with biliary fistulas in order to assess the potential of the two contrast agents for use in intravenous cholangiography. For any equimolar infusion rate, more iodoxamate was secreted in the bile than iodipamide was the same. At the constant basal bile flow maintained in these studies, there was no difference in the maximum biliary concentration of the two compounds. With the presently recommended doses, it is unlikely that iodoxamate will offer a striking improvement over iodipamide for intravenous cholangiography in patients with normal liver function.

The maximum biliary excretion rate of iotroxamide was found to be significantly greater than that of iodipamide in bile-fistula dogs. High bile salt excretion rates had no effect on the rate of biliary excretion of either compound, but the choleresis associated with greater bile salt excretion reduced the biliary concentration of both agents. Both are potent choleretics, stimulating about 23.5 ml of bile per mmole of contrast agent excreted in bile. This obligatory coupling of the contrast agents with water as they are excreted in bile imposes a limit on the maximum concentration that can be achieved in bile. Since iotroxamide is excreted more rapidly in bile than iodipamide for any equimolar plasma concentration, it may be a superior contrast agent for intravenous cholangiography.

Conflicting data have been reported concerning the optimum dose and rate of administration of iodipamide required to obtain maximum radiographic opacification of the biliary tree during intravenous cholangiography. Experiments were performed in dogs to determine the effect of plasma concentration on the excretion and concentration of iodipamide in the bile and urine during a steady state of infusion and excretion. The data indicate that a hyperbolic relation exists between the plasma concentration and both the biliary concentration and the total biliary excretion. A mathematical expression of these relations is presented. At low plasma concentrations, iodipamide was not excreted in the urine. However, at high plasma concentrations, urinary excretion increased sharply. It appears that a biliary concentration of iodipamide sufficient to achieve adequate radiographic visualization of the biliary tree can be obtained without significant renal excretion by constant infusion of iodipamide at an appropriate rate in dogs. Stepwise increase in the infusion rate until adequate radiographic visualization is obtained may be the best method for performing intravenous cholangiography to obtain visualization with the least amount of iodipamide in order to minimize toxicity.

Cholografin and Renografin 76 were studied to determine their effects on platelet function. In vitro platelet aggregation was significantly inhibited by at least 3.4 micron/ml Cholografin and 19.5 micron/ml Renografin 76. Patients who received Cholografin for intravenous cholangiography, and Renografin 76 for non-cardiac angiography, had low levels of plasma contrast agent, and hemostasis was clinically unimpaired. Patients who received Renografin 76 for cardiac angiography had inhibition of platelet aggregation at high levels of plasma contrast agent; there was no correlation with prolonged bleeding times, or with bleeding complications. High levels of plasma contrast agent may inhibit platelet aggregation in vitro and in vivo, although this may not be associated with clinically significant bleeding.