Iodine contrast agents

Idee JM, Pines E, Prigent P, Corot C. Allergy-Uke reactions to iodinated contrast agents. A critical analysis. Fundam Clin Pharmacol 2005 19 263-281. 

The analysis of X-ray contrast agents has not been described in too much detail in the hterature. Only scattered data for individual compounds can be found. In the following paragraphs, we will concentrate both on the determination of physicochemical characteristics, which allow for a classification of different contrast agents, e.g. into high and low-osmolar substances, and on the separation from by-products or biological material and on the determination of concentrations. Structural aspects of iodinated contrast agents have been described by Toennessen et al. [81]. 

Table 2. Physicochemical characteristics of iodinated contrast agents. Datahave been collected from refs. 94 and 129...

Jenkins et al. developed a capillary electrophoresis system for the measurement of iohexol as a marker of the glomerular filtration rate (GFR) with a run time of 5.25 min and a coefficient of variation (CV) of 4.3% at 80 mg L" [121]. The GFR, calculated from the plasma clearance, had a reproducibility of 5.47 %. A similar approach (liquid chromatography-mass spectrometry with positive electrospray ionization after enrichment by solid phase extraction) was applied by Putschew et al. for the determination of iodinated contrast agents in treatment plant effluents and surface waters [118]. 

Radioactively labelled contrast agents have been used to study biotransformation or biodegration processes. Rode and Muller described the transformation of iodinated contrast agents by microorganisms such as Trametes versicolor [121]. 

Iodinated contrast agents with polyhydroxylated carbon side-chains contain a number of asymmetric carbon atoms yielding numerous optical isomers which relate to each other as enantiomers or diastereoisomers. Sterically hindered non-asymmetric carbon or nitrogen atoms might result in additional asymmetry centres while the partial double bond character of the acyl-carbon-nitrogen bond of amide functions can lead to cisitrans isomerism. Such isomers are labelled rotamers when heating in solution is able to modify their ratio. Isomerism of iodixanol has been described by Priebe et al. [122], Fossheim et al. [123] and by Molander et al. [115]. 

Meyer DH (1999) The iodinated contrast agents future prospects. In Dawson P, Cosgrove DO, Grainger RG (eds) Textbook of contrast media. ISIS Medical Media,Oxford,p 239... 

Table 1. Selected liposome preparations with encapsulated iodinated contrast agents...

Leander et al. described ready-to-use liposomes that were effective and well tolerated in humans [61]. The iodinated contrast agent was the non-ionic dimer, iodixanol. The particle size of the liposomes was 350 nm with an iodine concentration of 70-80 mg mL encapsulated. They injected doses of 30, 70 or 100 mgl kg intravenously and found maximal enhancement values of 45 HU in the liver and 240 HU in the spleen. The uptake into these organs was not linealy correlated with the injected dose. No serious or unexpected adverse reactions were reported. Dose-dependent changes in leukocyte counts and body temperature were seen. 

Dy-EOB-DTPA). The second group is represented by liposomes with different extracellular iodinated contrast agents that are encapsulated and by PFOB. Efficacy does not seem to be an issue for these agents. The future will show whether their safety will be sufficient for further development. 

The fifth chapter is dedicated to macromolecular iodinated contrast agents with low dispersity. They can be utilized as blood-pool agents. The synthesis, analysis and pharmacokinetics of this class of compounds is summarized and their diagnostic impact is evaluated. 

The iodinated contrast agents, ipodate and iopanic acid are used in the treatment of hyperthyroidism. These drugs rapidly inhibit the conversion of T to T in the liver, kidney, brain and pituitary gland. 

Gadolinium chelates for MRI (SEDA 18, 446) (SEDA-20, 419) (SEDA-21, 475) (SEDA-22, 503) are inert, non-metabolized, small molecules, with essentially the same pharmacokinetic properties as the iodinated contrast agents. They are rapidly distributed in the extracellular fluid spaces, both intravascular and extravascular, although they do not cross the normal blood-brain barrier, and are almost entirely excreted by glomerular filtration, with no significant active tubular excretion or re-absorption. Hepatic excretion occurs in patients with... 

The use of gadolinium-based contrast agents as an alternative to iodinated contrast agents has been reported in a patient with a history of allergy to the latter (3). 

This case underlines the fact that there is still misunderstanding about the nephrotoxic potential of gadolinium-based contrast agents. They should not replace iodinated contrast agents in patients with renal insufficiency. The recommended doses of up to 0.3 mmol/kg will not give satisfactory radiographic diagnostic information in most cases. 

Exacerbation of a lupus-like illness after injection of iodinated contrast agents has been reported (SEDA-9, 411) (SEDA-19, 427). All iodinated contrast agents should be used with caution in patients with systemic lupus erythematosus and perhaps in other types of vasculitis. 

Lactic acidosis can occur after the use of intravascular iodinated contrast agents in patients taking metformin. Metformin is excreted by the kidneys, and renal insufficiency can lead to its retention, which can cause fatal lactic acidosis. The manufacturers have recommended that metformin should be withdrawn for 48 hours before and 48 hours after the administration of intravascular contrast media, which can cause renal damage, and treatment should not be restarted until normal renal function is confirmed. Reviews of reported cases of lactic acidosis after contrast administration have shown that there was pre-existing renal impairment in all cases. A retrospective evaluation of patients taking metformin who underwent... 

Weinstein GS, O Dorisio TM, Joehl RJ, Pokorney B, Koch KL. Exacerbation of diarrhea after iodinated contrast agents in a patient with VIPoma. Dig Dis Sci 1985 30(6) 588-92. 

Dewachter P, Mouton-Faivre C. Reactions severes avec les produits de contraste iodes I anaphylaxie est-elle responsable [Severe reactions to iodinated contrast agents is anaphylaxis responsible ] J Radiol 2001 82(9 Pt l) 973-7. 

Ridley LJ. Allergic reactions to oral iodinated contrast agents reactions to oral contrast. Australas Radiol 1998 42(2) 114-17. 

Chagnac Y, Hadani M, Goldhammer Y. Myasthenic crisis after intravenous administration of iodinated contrast agent. Neurology 1985 35(8) 1219-20. 

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