What is iohexol?

Iohexol: A Nonionic Contrast Medium Used for Radiographic Imaging and GFR Measurement

Iohexol is a nonionic, low-osmolality contrast medium primarily used for radiographic imaging procedures and measuring glomerular filtration rate (GFR). 1, 2

Chemical Properties and Composition

• Chemical structure: Iohexol (Chemical Abstract Services number 66108-95-0) is a triiodinated molecule with a molecular weight of 821.14 g/mol 1, 2
• Composition: Contains a benzene molecule with:
  • N-(2,3-dihydroxypropyl) carbamoyl groups at positions 1 and 3
  • Iodine atoms at positions 2,4, and 6
  • N-(2,3-dihydroxypropyl) acetamido group at position 5 1
• Formulation: Exists as a racemic mixture of isomers (endoiohexol and exoiohexol) 1
• Commercial preparations: Available as Omnipaque or Accupaque (GE Healthcare) in various concentrations:
  • Omnipaque 350: 755 mg iohexol/ml (350 mg iodine/ml)
  • Omnipaque 300: 647 mg iohexol/ml (300 mg iodine/ml)
  • Omnipaque 240: 518 mg iohexol/ml (240 mg iodine/ml)
  • Omnipaque 180: 388 mg iohexol/ml (180 mg iodine/ml)
  • Omnipaque 140: 302 mg iohexol/ml (140 mg iodine/ml) 1

Pharmacokinetics

• Distribution: After intravascular injection, iohexol distributes in the extracellular fluid compartment 2
• Metabolism: No significant metabolism, deiodination, or biotransformation occurs 2
• Excretion: Primarily excreted unchanged by glomerular filtration 2
  • Approximately 90% excreted within 24 hours
  • Peak urine concentrations occur within the first hour
  • Renal clearance: 120 (86-162) mL/min
  • Total body clearance: 131 (98-165) mL/min
  • Volume of distribution: 165 (108-219) mL/kg 2
• Protein binding: Low affinity for serum or plasma proteins; poorly bound to serum albumin 2
• Placental transfer: Crosses the placental barrier in humans by simple diffusion 2, 3

Clinical Applications

1. Radiographic Imaging

• Used as a contrast agent for computed tomography (CT) scans 1, 2
• Enhances imaging through augmentation of radiographic efficiency 2
• The degree of density enhancement directly relates to iodine content 2
• Peak contrast enhancement occurs 15-120 seconds after bolus administration 2

2. GFR Measurement

• Increasingly used as an exogenous marker for measuring GFR 1, 4
• Advantages over other markers:
  • Safe and inexpensive
  • Non-radiolabeled
  • Widely available
  • Samples can be frozen and assayed at a distance 1
• Plasma clearance method does not require timed urine collection 1
• Can be accurately used for GFR measurements even in severe renal impairment (<20 ml/min) 4

Safety Profile

• Adverse reactions: Lower incidence compared to ionic contrast media 5, 6, 7

  • Incidence of anaphylactoid reactions approximately 1% 8
  • Severe reactions occur in only about 0.04% of cases 8
  • In patients with previous reactions to ionic contrast media, iohexol significantly reduces repeat reaction rates (5.5% vs 16-44%) 5
  • Produces fewer deleterious hemodynamic and electrocardiographic changes than ionic agents 7

• Special populations:

  • Renal impairment: In severe renal impairment, excretion may be delayed and opacification of collecting systems may be inadequate 2
  • Pregnancy: Crosses the placental barrier and can enter the fetus in significant concentrations 2, 3

Important Considerations for Clinical Use

• For GFR measurement:

  • Standard dose: 5 ml of Omnipaque (typically 300 mg iodine/ml) 1
  • Blood samples should not be frozen before centrifugation to prevent cell lysis 1
  • Mild hemolysis doesn't significantly impact iohexol concentrations, but grossly hemolyzed specimens should be discarded 1
  • Samples can be stored at -20°C or -80°C for delayed analysis 1
  • Assays should have analytical imprecision <3% 1

• Laboratory considerations:

  • Iohexol should be assayed in accredited laboratories with quality control processes 1
  • Can be quantitated using high-performance liquid chromatography or chromatography-tandem mass spectrometry 1
  • Correct calibration is essential for accurate clearance calculation 1

• Misconceptions:

  • The concept of "iodine allergy" is scientifically inaccurate 8
  • No cross-reactivity exists between shellfish allergies and contrast media reactions 8

In summary, iohexol is a versatile nonionic contrast agent with applications in both diagnostic imaging and GFR measurement, with a favorable safety profile compared to ionic contrast media.