Iohexol

Iohexol is a nonionic, water‑soluble, iodinated radiographic contrast medium commonly employed in medical imaging procedures such as computed tomography (CT), angiography, urography, and arthrography. It enhances the contrast of vascular structures and organ systems by increasing the attenuation of X‑rays, thereby improving the visibility of anatomical details on radiographic images.

Chemical and Physical Properties

• IUPAC name: 1‑N‑(2,3‑Dihydroxypropyl)‑5‑[2‑(3‑acetyl‑2,4‑dihydroxy‑5‑methylphenoxy)‑ethoxy]‑3‑[2‑(4‑amino‑2‑hydroxy‑6‑methyl‑pyrimidin‑5‑yl)‑ethyl]‑2‑hydroxy‑benzene‑1‑carboxamide
• Molecular formula: C₁₉H₂₆I₃N₃O₉
• Molecular weight: 821.07 g·mol⁻¹
• Physical state: Colorless, sterile aqueous solution; typically supplied in concentrations of 240 mg I mL⁻¹ (300 mg I mL⁻¹, 350 mg I mL⁻¹) depending on the preparation.
• Osmolality: Varies with concentration; for the 240 mg I mL⁻¹ formulation, osmolality is approximately 640 mOsm kg⁻¹ at 37 °C.
• pH: Typically in the range 6.5–8.0.

Pharmacology
Iohexol exerts its contrast effect by virtue of the high atomic number of iodine, which strongly absorbs X‑ray photons. The compound is not metabolized appreciably; it remains unchanged in the plasma and is eliminated unchanged via renal excretion. The plasma half‑life is approximately 2 hours in individuals with normal renal function, with >90 % of the administered dose recovered in the urine within 24 hours.

Clinical Uses

• Intravenous (IV) administration: For enhancement in CT scans of the brain, chest, abdomen, pelvis, and vascular system.
• Intra‑arterial administration: During angiography and interventional radiology procedures to delineate arterial, venous, and capillary networks.
• Intrathecal and epidural administration: In select cases, such as myelography, using low‑osmolar formulations.
• Intra‑articular injection: For arthrography to assess joint spaces.
• Retrograde urography and cystography: For visualization of the urinary tract.

Safety and Adverse Effects
Iohexol is classified as a low‑osmolality, nonionic contrast agent, which generally confers a lower incidence of adverse reactions compared with older high‑osmolality ionic agents. Reported adverse events include:

• Mild reactions: Warmth, flushing, taste alteration, nausea, vomiting, and transient hypertension.
• Moderate reactions: Urticaria, pruritus, and bronchospasm.
• Severe reactions: Anaphylactoid responses, hypotension, bronchospasm requiring intervention, and rare cases of cardiovascular collapse.
• Nephrotoxicity: Contrast‑induced nephropathy (CIN) is a recognized risk, especially in patients with pre‑existing renal impairment, diabetes mellitus, or volume depletion. Preventive measures such as adequate hydration and use of the lowest effective dose are recommended.
• Other concerns: Iodine allergy, hyperthyroidism exacerbation, and potential for extravasation injury if administered intravenously.

Regulatory Status
Iohexol is approved for clinical use in many countries and is listed in pharmacopoeias. In the United States, it is marketed under the brand name Omnipaque® among others; in Europe and other regions, it is sold under various trade names. The drug is classified as a prescription medication and is subject to standard pharmacovigilance monitoring.

Manufacturing and Formulation
It is produced by iodination of a tri‑iodinated benzene ring followed by coupling to a nonionic, water‑soluble side chain that imparts high solubility and low viscosity. The final product contains the active ingredient in aqueous solution, buffered to maintain physiological pH, and may include sterile water for injection and, in some formulations, preservatives such as sodium chloride to adjust tonicity.

Pharmacokinetic Summary

Research and Development
Since its introduction in the early 1980s, iohexol has served as a reference standard for low‑osmolality nonionic contrast agents. Ongoing research focuses on optimizing dosing protocols to reduce renal risk, developing iso‑osmolar formulations, and investigating alternative routes of administration for specific diagnostic procedures.

References

• American College of Radiology (ACR) Manual on Contrast Media.
• European Society of Urogenital Radiology (ESUR) Guidelines on Contrast Media.
• FDA-approved prescribing information for Omnipaque®.
• Briguet, H., et al. “Pharmacokinetics of Iohexol in Renal Impairment.” Radiology 1995.
• Lallemand, F., et al. “Adverse Reactions to Nonionic Iodinated Contrast Media.” Radiographics 2008.

This entry reflects the current state of knowledge up to the cutoff date and does not incorporate unpublished or speculative data.