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PubMedDate not supplied

Iosulamide: a new intravenous cholangiocholecystographic medium.

Iosulamide is a bis-benzoic analogue of metrizoate that shows clear advantages in animal tests over meglumine iodipamide. The intravenous toxicity of iosulamide meglumine is considerably lower than that of iodipamide (Cholografin) in the mouse and rat. The LD50 in mice for iosulamide meglumine is 11,500 +/- 844 mg free acid/kg and for iodipamide is 2380 +/- 290 mg free acid/kg. A threefold difference in toxicity was seen in rats; the LD50 for iosulamide meglumine is 13,600 +/- 1710 mg free acid kg and for iodipamide is 4430 +/- 310 mg free acid/kg. Iosulamide is a highly effective contrast agent for cholangiocholecystographic visualization in cats and monkeys. speed and degree of opacification are equivalent to that of iodipamide at equimolar doses. Studies of biliary and urinary excretion patterns indicate iosulamide is rapidly excreted compared to iodipamide, while at the same time providing equal concentrations in bile on an mg/ml bile basis. A more efficient blood to bile clearance rate and a shorter blood half-life for iosulamide may account for the lower circulating blood levels and rapid total excretion compared to iodipamide. Iosulamide's rapid blood-bile clearance coupled with its extremely low toxicity may allow rapid administration of high doses, affording superior visualization and safety compared to iodipamide. It may also provide visualization of the liver parenchyma with computerized axial tomography, due to the pharmacokinetic profile that provides for high liver clearance but low blood levels. The emetic potential of iosulamide meglumine is quite low compared to iodipamide. Iosulamide meglumine also lacks hypotensive activity. Little or no effect on blood pressure was seen with iosulamide meglumine in cats or monkeys, whereas iodipamide caused marked transient, or sustained, reductions. Iosulamide meglumine did not produce significant toxic effects when administered as single daily intravenous injections to albino rats for three weeks, or in 10-minute intravenous infusions to rhesus monkeys 10 times in 14 days. Clinical trials with iosulamide are under way.

Animals↗
PubMedDate not supplied

The biliary and urinary excretion and the choleretic effect of ioglycamide in dogs.

The biliary and urinary excretion and the choleretic effect of ioglycamide were studied in unanesthetized bile fistula dogs using stepwise increasing infusion rates to obtain multiple steady states. The results are compared with data from previously reported experiments in the same animals using iodoxamate and iodipamide. The rate of biliary excretion and the choleretic effect of ioglycamide are similar to those of iodipamide and iodoxamate. Like iodipamide and iodoxamate, the relation between infusion rate or plasma concentration and biliary excretion or concentration of ioglycamide are hyperbolic and can be fitted to saturation kinetics. Quantitatively, the excretion of ioglycamide and iodipamide are virtually identical. However, for any equimolar infusion rate or plasma concentration, more iodoxamate than ioglycamide is excreted in the bile. Despite the greater biliary excretion of iodoxamate, the maximum biliary concentration of ioglycamide, iodipamide, and iodoxamate is the same at low basal bile flow because the choleretic effects of the three compounds are equal. The data suggest that, theoretically, with any equimolar dose ioglycamide will be identical to iodipamide as a contrast material for intravenous cholangiography, but that iodoxamate may be superior to ioglycamide because more iodoxamate is excreted in the bile. This advantage of iodoxamate might become apparent clinically in patients with high basal bile flow or if smaller doses of the contrast material are used. However, at the presently recommended doses of the two compounds, it is unlikely that the use of ioglycamide for intravenous cholangiography will be any different than iodoxamate.

Animals↗
PubMedDate not supplied

Cholangiographic excretion studies. Solu-Biloptin and Biligrafin comparison.

The biliary concentration and output of two cholangiographic agents, Solu-Biloptin (calcium ipodate) and Biligrafin (meglumine iodipamide), were compared in labrador dogs. The maximum output of ipodate was approximately 20 mumol/min compared with 16 mumol/min for iodipamide. The maximum bile iodine concentration with both ipodate and iodipamide was similar (18-20 mgI/Ml) but the molar concentration of ipodate was almost twice that of iodipamide. Iodipamide was found to be much more choleretic, producing 0.025 ml of bile/mumole excreted compared with 0.009 ml/mumole for ipodate. Compared with iodipamide the lower choleretic effect and higher molar concentration of ipodate suggests that hepatic conjugation of the oral agent may permit its excretion in bile salt micelles.

Animals↗
PubMedDate not supplied

Intravenous cholangiography in different degrees of common bile duct obstruction. An experimental study in the dog.

A total of 83 cholangiograms was performed in three cholecystectomized dogs equipped with Thomas cannulas through which complete and different degrees of incomplete common bile duct obstruction were produced. With incomplete common bile duct obstruction, the iodine concentration in the bile necessary for radiographic visualization of the common duct was always obtained for all three tested iodipamide dosages of .3, .6, and 1.2 ml/kg, infused over 30 minutes. The largest dose resulted in the highest biliary iodine concentrations. With increasing obstruction, an increasing delay of the biliary iodipamide excretion was noted. With complete common bile duct obstruction the iodine concentration in the bile necessary for radiographic visualization of the common duct was never obtained, even with an iodipamide dose increased to 1.8 ml/kg and/or prolongation of the contrast material infusion time from 30 minutes to 2 and 6 hours. Nevertheless, the highest biliary iodine concentration in complete common bile duct obstruction resulted with the largest iodipamide dose (1.8 ml/kg) and the shortest infusion time (30 minutes).

Animals↗
PubMed1986

Effects of intravenous radiographic contrast media on the blood pressure and on factors of the contact activation system in the rat.

Blood pressure (BP), plasma prekallikrein (PK), and the extent of activation of factor XII (XII-ACT) were studied after the intravenous injection into rats of dextran (Macrodex), the ionic radiographic contrast substance iodipamide (Biligrafin), or the non-ionic contrast substance iohexol (Omnipaque). After acetone activation plasma kallikrein was assayed as plasminogen activator, BAEe esterase or S-2302 amidase, and factor XIIa was assayed as kaolin-activated prekallikrein activator. Dextran induced a strong and lasting hypotension, preceded by significant lowerings in PK and XII-ACT. Iodipamide induced a rapid and dose dependent BP fall, no change in plasma PK, but a slightly reduced XII-ACT. Iohexol induced no significant alterations, neither in BP, nor in plasma parameters. Pretreatments of the rats with iodipamide abolished the dextran-induced reductions in PK and XII-ACT, and almost blocked the fall in BP. We conclude that the ionic contrast substance iodipamide is capable of blocking dextran shock in the rat by preventing an activation of the contact activating system in plasma.

Anaphylaxis↗
PubMed1980

Intravenous cholangiography: experimental evaluation of the time-density-retention concept.

The time-density-retention concept was evaluated in chronic cholecystectomized bile fistula dogs with normal hepatic function, partial common bile duct obstruction, and hepatic parenchymal disease using either iodipamide or iodoxamate. In all investigated conditions, the maximum biliary iodine concentration was found earlier with iodoxamate than iodipamide but the difference was only significant in partial common bile duct obstruction. In this condition a significant delay in attaining the maximum biliary iodine concentration was found with iodipamide but not with iodoxamate. It is concluded that the time-density-retention concept represents a valid radiographic criterion for the diagnosis of partial common bile duct obstruction in cholecystectomized or cystic duct occluded subjects when iodipamide but not iodoxamate is used as contrast agent.

Animals↗
PubMed1982

Effect of organic anions on biliary lipids in the rat.

Bile salts enhance the biliary secretion of phospholipid and cholesterol. Other amphipilic molecules, organic anions, are secreted into bile as well. We studied the effects of bilirubin and iodipamide, two chemically dissimilar organic anions, on biliary lipid secretion in the rat. We infused bile salt pool-depleted rats with a stepwise infusion of taurocholate and a constant infusion of organic anion. Both organic anions markedly inhibited the biliary secretion of phospholipid and cholesterol without affecting bile salt secretion. This inhibition, at least with iodipamide, was dose-dependent and fully reversible. Using tritiated water as a precursor, we measured hepatic and biliary cholesterol synthesis in the presence or absence of an iodipamide infusion to see if decreased lipid synthesis could explain decreased secretion. Despite the marked reduction in biliary cholesterol secretion, the specific activity of biliary cholesterol was unchanged during an iodipamide infusion. We suggest that organic anions interfere with the assembly of the biliary mixed micelle resulting in micelles that are deficient in phospholipid and cholesterol.

Animals↗
PubMed1975

[Slow infusion cholangiography in jaundice. An experimental study in the dog].

56 intravenous cholangiograms were performed in eleven dogs with either advanced hepatic damage or complete common bile duct obstruction. If radiographic visualization of the biliary system did not occur within 8 hours after a 30 minute infusion with 0.6 ml/kg iodipamide 52%, the result could not be improved by just extending the infusion time to 2 and 6 hours. However, a slight improvement was obtained, when the iodipamide dose was increased up to 1.8 ml/kg. Nevertheless we do not recommend a massive increase of the dose in the icteric patient, because it is likely that the risk of toxic side effects increases with an increasing iodipamide dose.

Animals↗
PubMed1979

[Intravenous cholangiography in hyperbilirubinaemia (author's transl)].

The effect of bilirubin on biliary and renal excretion of methylglucamine-iodipamide at an infusion rate of 1.3, 2.6 and 5.2 mu mol/min/kg was studied by intravenous injection into five dogs with normal liver functions and chronic duodenal fistulas. Unconjugated bilirubin administered in a dose of 0.1 mu mol/min/kg reduced biliary iodipamide excretion and concentration significantly, but did not affect renal contrast material excretion. This indicates that the unsatisficatory radiological results of intravenous cholangiography in hepatic and obstructive jaundice depend not only on the reduced excretion capacity of the liver, but are also due to a direct inhibitory effect of bilirubin on biliary contrast material excretion. In the presence of hyperbilirubinaemia, the highest iodine concentrations in the bile were obtained with the highest iodipamide serum levels; a reduction in contrast material dose or prolongation of the period of contrast material infusion therefore does not appear to be indicated in jaundiced patients.

Animals↗
PubMedDate not supplied

Activation of serum complement by contrast media.

Evidence is presented for the activation of serum complement by contrast media, in vitro and in vivo. Activation as a function of concentration was measured and the increasing order of effectiveness was found to be metrizamide, iothalamate, diatrizoate, acetrizoate, iodipamide and iopanoate. This order is the same as for protein binding and enzyme inhibition. The activation mechanism for iodipamide, and by inference for the other compounds, does not involve gamma-globulin aggregation. Serial daily injections in normal dogs resulted in substantial declines in serum complement over several days. Guinea pigs which were depleted of serum complement with cobra venom factor were found to be no less sensitive to lethal doses of iodipamide than those with normal complement. Implications of these findings are discussed.

Acetrizoic Acid↗