Biliary Contrast Agent Research Articles

Choledocholithiasis: diagnosis with oral-contrast-enhanced CT cholangiography.

The objective of this investigation was to assess the performance of helical CT cholangiography after administration of an oral biliary contrast agent for the diagnosis of choledocholithiasis. Helical CT cholangiography was performed on 31 patients referred for endoscopic retrograde cholangiography of suspected choledocholithiasis. Iopanoic acid (6 g) was administered orally 8-12 hr before acquisition of helical CT cholangiograms. Three-dimensional and two-dimensional reformations were generated from a set of axial source images. Two radiologists independently interpreted the helical CT cholangiograms. Sensitivity and specificity were calculated using findings on retrograde cholangiography as the standard of reference. In addition, interobserver agreement was determined using kappa statistics. Our patients had no adverse reactions to iopanoic acid. The degree of biliary opacification was sufficient to perform three-dimensional and two-dimensional reconstructions in 29 patients (93.5%). Two patients were excluded from statistical analysis because cannulation of the common bile duct during retrograde cholangiography failed. Findings on endoscopic retrograde cholangiography in the remaining 29 patients were the following: choledocholithiasis (n = 14), common bile duct dilatation with no stones (n = 11), and normal bile ducts (n = 4). Sensitivity and specificity of oral-contrast-enhanced CT cholangiography for detection of choledocholithiasis were 92.9% (95% confidence interval [CI], 66.1-99.8%) and 100% (95% CI, 78.2-100%), respectively, for observer 1 and 85.7% (95% CI, 57.2-98.2%) and 100% (95% CI, 78.2-100%), respectively, for observer 2. Interobserver agreement was .92 (excellent). Helical CT cholangiography performed after oral administration of iopanoic acid appears promising for diagnosis of choledocholithiasis.

An overview of the clinical pharmacokinetics of x-ray contrast media.

Pharmacokinetic studies of contrast media are usually performed as preclinical trials in anaesthetised animals; however, results in humans have also been reported for this type of compounds. This paper reviews the existing data about x-ray contrast media in humans. In some cases, animal data are used in areas where no human data are available. The administration of contrast media is generally made via the intravenous, intra-arterial or intrathecal route. Diagnostic procedures are based on differential distribution to organs and between normal and abnormal tissue. Data are available for iodixanol, iohexol, iopamidol, iopromide, iothalamate and ioxaglate, but the kinetic distribution of all contrast media is similar. With the exception of biliary contrast agents, all compounds display limited plasma protein binding and do not undergo biotransformation. From the pharmacokinetic viewpoint, the main area of interest for these compounds is elimination. The majority of the data were obtained with iopamidol (of which 66 to 72% of the dose is excreted in the urine), iohexol, ioxaglate and iopromide. Some studies were performed in patients with renal impairment: in this case, metabolic clearance was abnormally elevated, suggesting the existence of significant compensatory factors such as hepatic metabolism, enterohepatic circulation and biliary elimination. New compounds, such as iodinated polymers for x-ray perfusion imaging and iopromide- or metrizamide-containing liposomes allowing liver enhancement are discussed.

Limited usefulness of carbon dioxide as a contrast agent for cholangiography.

Carbon dioxide (CO2) was unsuccessfully used as a biliary contrast agent in 9 of 10 patients undergoing percutaneous transhepatic cholangiography prior to biliary drainage. The technique involved hand injection of 10-20 cc CO2 through the Chiba needle in an attempt to fill preferentially the anterior biliary radicals. Although CO2 remains a useful agent in many instances, particularly for percutaneous nephrostomy, its usefulness in the biliary tract is severely limited.

Polarographic Determination of Biliary Contrast Agents

Abstract A simple polarographic method suitable for the determination of BILIGRAM, an iodinated biliary contrast agent acting as a specific probe of Carbon-Iodine bonds, is described, Its application to the quantitative analysis of Albumin unbound and overall BILIGRAM is reported.

Time-density evaluation of the liver after iosulamide meglumine: a tissue-specific CT contrast agent.

Iosulamide meglumine, a new intravenous biliary contrast agent, was evaluated as a potential hepatic contrast agent utilizing computed tomographic scanning. Time-density data in dogs were generated following 56.7 and 75.6 mg iodine/kg body weight. The iodine was administered both as an iosulamide meglumine bolus injection and a 0.77 ml/min infusion. The greatest increase in x-ray attenuation (24 HU) was observed within 45 minutes after the 75.6 mg iodine/kg body weight infusion technique, which resulted in excellent hepatic opacification. The long duration of increased x-ray attenuation of hepatocytes produced by iosulamide meglumine would be useful in the CT detection of hepatic mass lesions which do not contain normally functioning hepatic cells.

Optical Studies on Interaction of Biliary Contrast Agents with Native and Modified Human Serum Albumin

The interaction of two homologous series of biliary contrast agents with native human and bovine serum albumin and with modified human serum albumin was investigated using circular dichroism and equilibrium dialysis. For most derivatives, extrinsic Cotton effects were observed for the interaction with both albumins. In some cases, these effects were strongly affected by only small changes in the chemical structure of the drugs. These large differences in extrinsic Cotton effects can be explained by definite effects of the chemical structures on the binding site selectivity of some drugs. For example, iopodate preferentially binds to the warfarin binding site of human Scrum albumin, while an ethyl group into the propionic acid side chain reduces the affinity for the warfarin site but strongly increases the affinity for the diazepam binding site of human serum albumin.

The binding of intravenous and oral biliary contrast agents to human and bovine serum albumin.

The binding of two homologous series of oral and intravenous biliary contrast agents to human and bovine serum albumin was investigated using the gel filtration technique. All intravenous compounds are bound to human serum albumin via one high affinity and several low affinity binding sites. Within the concentration range investigated, about 3--5 high affinity binding sites for the oral compounds were found on human serum albumin. In general, the intravenous compounds have a greater affinity for human serum albumin than the oral compounds. No significant differences were found for the binding of the oral compounds to human or bovine serum albumin, while the intravenous compounds have a higher affinity for bovine than for human serum albumin. The significance of the plasma protein binding of the biliary contrast agents for the hepatic uptake is discussed.

Effect of ioglycamide (Biligram) on bile flow and biliary lipid secretion in man.

Twenty-one anicteric patients with a t-tube in situ were studied between the ninth and 11th postoperative days. Eleven patients were given an intravenous infusion of the biliary contrast agent ioglycamide (Biligram), while the other 10 acted as controls. Bile flow was recorded and the biliary concentrations of ioglycamide, bile salt, phospholipid, and cholesterol estimated in the two groups. The biliary excretion of ioglycamide was associated with a significant choleresis which was probably due to the obligatory coupling of the osmotically active contrast agent molecules with water. Biliary ioglycamide excretion did not significantly alter bile salt secretion rates. In contrast, the biliary secretion of both phospholipid and cholesterol was significantly lowered (P less than 0.001). Unlike chenodeoxycholic acid, ioglycamide significantly reduced bile acid independent cholesterol secretion (P less than 0.01), although secretion rate in terms of mumol of bile acid was essentially unchanged.

Pharmacology and physiology of the biliary radiographic contrast materials

1. (1) Solubilization of Telepaque in the intestine is a limiting factor in the rate of intestinal absorption. Bilopaque and Oragrafin are more water-soluble and appear to be better absorbed than Telepaque. 2. (2) Bile salts in the intestinal lumen increase the solubility of Telepaque. Therefore, a fatty meal administered with the Telepaque is desirable to evacuate bile salts from the gallbladder into the intestine. This is not required for the more water-soluble agents, Bilopaque and Oragrafin. 3. (3) The degree of protein binding of the contrast agents can be related to the degree of toxicity. Cholografin is the most highly bound and is the most toxic. 4. (4) Hepatic receptor proteins may specifically bind the biliary contrast agents. This may be the reason that the renal contrast materials are poorly excreted in bile compared to the biliary contrast agents. 5. (5) Telepaque is conjugated in the liver with glucuronide making the compound more soluble in bile. This prevents precipitation of Telepaque in the gallbladder and avoids reabsorption from the intestine. 6. (6) The biliary excretion of Telepaque is facilitated by bile salts. Therefore, the administration of a fatty meal with Telepaque not only increases the rate of intestinal absorption of Telepaque but also the rate of biliary excretion. 7. (7) The rate of biliary excretion of both the oral and the intravenous contrast agents appears to be limited by a hepatic transport maximum. Above a certain dose, increased amounts of the contrast agents do not result in more rapid excretion of the agents into bile. Rapid infusion of intravenous contrast agents results in high plasma concentration and greater urinary excretion, without increasing the biliary excretion. It does not appear to be indicated in clinical practice. 8. (8) The biliary concentration of the contrast agents used for intravenous cholangiography is determined by their rate of biliary excretion, the choleretic effect of the contrast agent, and factors that determine the rate of basal bile flow. Fixed coupling of water with the biliary excretion of these contrast agents imposes an inherent limitation on the concentration of the contrast agent in bile. It appears that the biliary concentration of the intravenous contrast materials can be increased by having the patient fast prior to intravenous cholangiography. This decreases the enterohepatic circulation of bile salts and the rate of bile-salt-dependent bile flow. 9. (9) Failure of the gallbladder to visualize after administration of Telepaque when there is adequate biliary excretion may be due to cystic duct obstruction, failure of the inflamed gallbladder mucosa to reabsorb water, or reabsorption of the contrast agent by the diseased gallbladder mucosa. 10. (10) Maximum concentration of Telepaque occurs at 14–19 hr after ingestion. It is at this time that radiographs of the gallbladder should be made. With Bilopaque, peak concentration occurs at 10 hr so radiographs can be made earlier when Bilopaque is used.

Cholecystography after Rectal Administration of Ipodate Salts

X-ray examination of the biliary system is often necessary in an acutely ill patient. Oral cholecystography and cholangiography may fail in adynamic ileus, upper intestinal obstruction or inflammatory disease, or vomiting which interferes with absorption of the contrast material from the upper intestinal tract. An intravenous study may be contraindicated because of previous reactions. The rectal route of administration of biliary contrast material offers an alternative approach and led to our evaluation of salts of Ipodate.2 Since the venous drainage of both the upper and lower intestinal tracts is mainly through the portal system, the rectal administration of biliary contrast agents anatomically favors the same venous route to the liver as does the oral. The clinical, pharmacologic, and chemical properties of the salts of Ipodate have been reported by several investigators (3–6). The structural formulas of these salts are shown in Figure 1. Because both the sodium and calcium salts of Ipodate are heat-sensitive and decompose at room temperature when in solution or suspension, they must be freshly prepared before administration. Following the oral intake of these salts, unaltered forms are found in the urine and the bile (48 per cent excreted in the urine in twenty-four hours). Excretion products in the form of metabolites with an intact ring structure and strongly bound iodine are found chiefly in the bile and in the urine. Fecal excretion is small (4.8 per cent). Maximum blood concentrations following oral administration are reached in two to three hours. After twenty-four hours only a minute amount can be measured in the blood stream (0.4 per cent). Material and Methods Thirty-five examinations were performed in 34 subjects (TABLE I). These patients were in no distress, and for the most part they were recovering from elective nonbiliary surgery; in a few, symptoms suggested biliary-tract disease. From a plastic compressible container a fresh preparation of a 60 cc aqueous solution of 6 g of sodium Oragrafin was introduced rectally in 17 cases; a fresh preparation of 6 g of calcium Oragrafin in 18. Each patient was urged to retain the contrast material until the examination was completed. Films were exposed at intervals until the biliary system had been visualized adequately or until six hours had elapsed from the time of administration of the contrast medium. Results Rectal retention was definitely more successful with the calcium Oragrafin than with sodium Oragrafin (Table II). Nine of the 17 subjects receiving the sodium Oragrafin expelled the contrast agent prematurely, but 16 retained it for at least thirty minutes. Only 2 of those receiving the calcium preparation expelled it prematurely. Over 90 per cent of the patients had an urge to evacuate, regardless of the contrast agent. The two materials are compared as to visualization of the biliary system in Table III.