Introduction

Iodixanol (Figure 1) is an iso-osmolal nonionic dimeric hydrophilic contrast agent. It has similar diagnostic efficacy to that of other iodinated contrast media. Because of its physical properties, iodixanol would be expected to produce a lower incidence of adverse events than other nondimeric contrast media. Indeed, pharmacodynamic studies indicate that iodixanol has fewer cardiovascular effects, causes less renal damage and is associated with similar or smaller changes to the blood brain barrier and neurological function when compared with nondimeric nonionic contrast media.In clinical trials, iodixanol had a similar tolerability profile to other nonionic contrast media but induced fewer adverse events than ioxaglate. Iodixanol appears to have an advantage over other contrast media in that it generally causes less frequent and less intense discomfort on injection. However, in common with other newer, and usually non ionic, contrast media, iodixanol is expensive. Studies investigating other non ionic contrast media (but not iodixanol) have shown that it is not cost-effective in all patients to replace older, usually ionic, contrast media with the more costly newer alternatives.Nonetheless, in selected patients who are considered at increased risk of contrast medium-associated adverse events, non ionic agents should be used. Iodixanol, with its lower intensity (and possibly frequency) of discomfort, may be a preferred option in these patients.[1]

Physical Properties

In addition to chemotoxicity, adverse events associated with contrast media are related to increases in osmolality and ionicity. Iodixanol is a dimeric nonionic contrast medium with lower osmolality and a higher iodine ratio than other nondimeric contrast media. Iodixanol has 9 hydroxyl groups and no carboxyl groups;presence of these groups is associated with reduced and increased toxicity, respectively.

PharmacodynamicProperties

Iodixanol produced similar angiographic attenuation, indicating similar diagnostic efficacy, to ioxaglate and iohexol in animals or an experimental circulation model. Contrast media have been associated with several adverse events affecting the cardiovascular system. However, injection of iodixanol into the coronary arteries of dogs with or without left ventricular failure does not cause depression of myocardial function. Transient alteration in cardiac parameters and ventricular tachycardia or fibrillation occur at a lower frequency and/or intensity than similar effects produced by iohexol, iotrolan (another hexaiodinated iso-osmolar contrast medium), ioxaglate or iopamidol. Iodixanol and iotrolan produce similar haemodynamic changes in pigs. Although intra-arterial injection of iodixanol 320 mgI/ml causes undesirable peripheral vasodilation in patients undergoing femoral arteriography, studies conducted in dogs or rabbits showed that iodixanol induced significantly smaller changes in blood flow than the same iodine concentrations of iohexol, iopentol, iopromide or metrizoate. Iodixanol, iopamidol, iopentol and iohexol all reduced erythrocyte aggregation in vitro by a similar extensive amount, but diatrizoate induced significantly more erythrocyte rigidification. The nonionic contrast media also induced morphological changes in erythrocytes with stomatocyte and echinocyte deformation occurring. However, iodixanol was the only agent that did not produce desiccocytes. Leucocyte phagocytosis, adherence and degranulation were also inhibited by contrast media, with iodixanol having the least effect.[1-2]

Pharmacokinetic Properties

Iodixanol has a pharmacokinetic profile similar to that of many other nonionic contrast media. After intravenous injection of iodixanol in healthy volunteers,peak serum iodixanol concentrations are rapidly achieved. Serum concentrations then decrease biexponentially: little drug is detected 24 hours after administration. Iodixanol distributes only in the extracellular fluid. Distribution half-life(t_I/2α), elimination half-life (t_I/2β) and apparent volume of distribution are not dose-dependent, with mean values of 0.43 and 2.18 hours and 0.275 L/kg, respectively, for iodixanol 0.3 to 1.2 gl/kg.

Iodixanol is not metabolised and is predominantly excreted in the urine by glomerular filtration. At least 97% of an injected dose is excreted unchanged in the urine within 24 hours and 1.2% is excreted unchanged in the faeces within 72 hours.The pharmacokinetic profile of iodixanol in elderly patients appears to be affected more by renal function than age. Iodixanol has similar distribution pharmacokinetics in patients with stable but severely impaired renal function (serum creatinine level >400μmol/L or creatinine clearance <20 ml/min) to that observed in healthy volunteers. However, elimination is slower: mean t_1/2β of the drug is prolonged and renal clearance is reduced. Over 5 days, 76.1 % of the administered iodixanol dose is excreted renally (via glomerular filtration) and 8.2% is recovered in the faeces of patients with renal impairment.

Diagnostic Efficacy

Iodixanol has been evaluated for use in endoscopic retrograde cholangiopancreatography, cardioanglography, cerebral angiography, urography and aortofemoral angiography. It has also been investigated for use in patients undergoing computed tomography. In general, diagnostic efficacy is achieved in almost all patients given iodixanol at concentrations of 270 or 320 mgI/ml. In most clinicaltrials, contrast media were preheated to 37°C before injection.

Iodixanol 270 and/or 320 mgI/ml have similar overall efficacy (pyelographic density and overall diagnostic information) to iopamido1 300 mgI/ml and iohexol 300 mgI/ml in patients undergoing intravenous urography. Two-fold dilutions of iodixanol 200 or 270 mgI/ml also demonstrated efficacy in a Japanese study of60 patients undergoing retrograde urethrography. In patients undergoing computed tomography of the body, iodixanol had similar efficacy to iohexol orioxithalamate.[1]

For more information, please refer to reference 1.

References

[1]Spencer CM, Goa KL. Iodixanol. A review of its pharmacodynamic and pharmacokinetic properties and diagnostic use as an x-ray contrast medium. Drugs. 1996;52(6):899-927. doi:10.2165/00003495-199652060-00013

[2]Fountaine H, Harnish P, Andrew E, Grynne B. Safety, tolerance, and pharmacokinetics of iodixanol injection, a nonionic, isosmolar, hexa-iodinated contrast agent. Acad Radiol. 1996;3 Suppl 3:S475-S484. doi:10.1016/s1076-6332(05)80362-9