Iohexol

The steric bulk of the three iodine atoms in the 2,4,6-triiodoben2ene system and the amide nature of the 1,3,5-substituents yield rotational isomers of the 5-A/-acyl-substituted 2,4,6-triiodoisophthalamides. Rotational motion in the bonds connecting the side chains and the aromatic ring is restricted. These compounds also exhibit stereoisomerism when chiral carbon atoms are present on side chains. (R,5)-3-Amino-l,2-propanediol is incorporated in the synthesis of iohexol (11) and ioversol (12) and an (3)-2-hydroxypropanoyl group is used in the synthesis of iopamidol (10). Consequendy, the resulting products contain a mixture of stereoisomers, ie, meso-isomers, or an optical isomer. 

Most contrast agents elicit nephrotoxicity because they are primarily excreted by the kidneys. However, when administered in small doses, they constitute a rich source of GFR markers. The two major classes of contrast agents that are finding clinical utility as GFR markers are iodinated aromatic compounds and metal complexes. lodinated aromatics such as iohexol and iothalamate (Fig. 13) are commonly used as contrast agents for computed tomography (GT). They also have pharmacokinetics similar to inulin and hence are useful indicators of renal status [215]. The iodinated molecules used for GFR measurements consist of a triiodo-benzene core and hydrophilic groups to enhance solubility in aqueous medium. 

Fig. 6. Route of synthesis of nonionic contrast agents, a Synthesis of iohexol with a symmetrical structure. R = R = 2,3-propandiol.b Synthesis of iopromide with an unsymmetrical structure. Ri = methyl. R2 = 2,3-propandiol. R2=acylated 2,3-propandiol...

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]. 

The aggregation of metrizamide in solution further reduced its osmolality to about 485 mOsm kg at 300 mgl mL [ 1 ]. Unfortunately, this agent could not be sterilized by autoclaving and, consequently, had to be lyophilized and reconstituted extemporaneously. In the mid-1970s, stable nonionic compounds such as iopamidol or iohexol superseded metrizamide. Further improvement was reached by stabilization of the hydrophilic sphere against external disruption, as shown with iobitridol [2]. 

Table 7. Effects of P743 and iohexol on histamine and leukotriene B4 release by isolated RBL-2H3 mast cells and cellular viability (MTT test)...

The effects of the RCBPA P743 and the SCBPA P840 on in vitro fibroblast viability were similar to those of iohexol (Table 8). 

Table 8. Inhibitory concentration 50% of P743, P840 and iohexol on mouse L-929 fibroblasts (MTT test)...

The CT behaviour of three alkyl esters or amides of diatrizoic acid (Fig. 1) in rabbits after i.v. injection of 3 mL kg (89 mgl mL ) was reported by Gazelle in 1994 [28]. The particles had sizes of 200-300 nm. The ester compound with the short alkyl chain circulated for a long time in the blood, and the ester with the longer chain was rapidly taken up by the Ever achieving CT densities in this organ of more than 225 HU. The amide showed a blood-pool behaviour similar to that of the short-chain ester. The ethyl ester of diatrizoic acid (EEDA), formulated as a nanoparticulate contrast agent with a diameter of 200 nm, was positively tested in a rabbit model with Ever abscesses [30]. EEDA proved to be superior to iohexol in detecting these abscesses. 

Leander P, Golman K, Strande P, Klaveness J, Besjakov J, Fait K (1993) A comparison between lEEC, a new biodegradable particulate contrast medium, and iohexol in a tumor model of computed tomography imaging of the liver. Invest Radiol 28 513... 

Gazelle GS, Wolf GL, Mclntire GL, Bacon ER, Na G, Halpern EF, Toner JL (1995) Hepatic imaging with io dinated nanoparticJes a comparison with iohexol in rabbits. Acad Radiol... 

Bergman A, Sundin A, Magnusson A (1997) An iodinated lipid emulsion for CT of the liver. Comparison with iohexol in the detection of experimental hepatic metastases. Acta Radiol 38 55... 

Many radiocontrast media contain iodine. These include iodixonal, iohexol, iomeprole, iopamidole, iopanoic acid, iopitridole, iopromide, iothalamate, iotrolan, ioversol, and ioxaglate. 

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