Iodixanol - How It Works
Clinical pharmacology details from the US FDA-approved label: how Iodixanol works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Intravascular injection of iodixanol opacifies vessels in the path of flow of the contrast agent, permitting visualization of internal structures. In imaging of the body, iodinated contrast agents diffuse from the vascular into the extravascular space. In a normal brain with an intact blood-brain barrier, contrast does not diffuse into the extravascular space. In patients with a disrupted blood- brain barrier, contrast agent accumulates in the interstitial space in the region of disruption.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Intravascular injection of iodixanol opacifies vessels in the path of flow of the contrast agent, permitting visualization of internal structures.
In imaging of the body, iodinated contrast agents diffuse from the vascular into the extravascular space.
In a normal brain with an intact blood-brain barrier, contrast does not diffuse into the extravascular space.
In patients with a disrupted blood- brain barrier, contrast agent accumulates in the interstitial space in the region of disruption.
12.2 Pharmacodynamics Following administration of iodixanol, the degree of enhancement is directly related to the iodine content in an administered dose.
Peak iodine plasma levels occur immediately following rapid injection.
The time to maximum contrast enhancement can vary, depending on the organ, from the time that peak blood iodine concentrations are reached to one hour after intravenous bolus administration.
When a delay between peak blood iodine concentrations and peak contrast is present, it suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine-containing medium within the lesion and outside the blood pool.
For angiography, contrast enhancement is greatest immediately (15 seconds to 120 seconds) after rapid injection.
Iodinated contrast agents may be visualized in the renal parenchyma within 30 to 60 seconds following rapid intravenous injection.
Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1 to 3 minutes, with optimum contrast occurring within 5 to 15 minutes.
12.3 Pharmacokinetics Distribution In an in vitro human plasma study, iodixanol did not bind to protein.
The volume of distribution in adults was 0.26 L/kg body weight, consistent with distribution to extracellular space.
Elimination In 40 healthy, young male volunteers receiving a single intravenous administration of iodixanol in doses of 0.3 gram Iodine/kg to 1.2 gram Iodine/kg body weight, the elimination half-life was 2.1 hr. (± 0.1).
Renal clearance was 110 ± 14 mL/min, equivalent to glomerular filtration (108 mL/min).
These values were independent of the dose administered.
Metabolism Iodixanol does not undergo metabolism.
Excretion In adults, approximately 97% of the injected dose of iodixanol is excreted unchanged in urine within 24 hours, with less than 2% excreted in feces within five days post-injection.
Specific Populations Pediatric: Forty pediatric patients ≤12 years old, with renal function that is normal for their age, received multiple intra-arterial administrations of iodixanol in doses of 0.32 gram Iodine/kg to 3.2 gram Iodine/kg body weight.
The elimination half-lives for these patients are shown in Table 5.
Pharmacokinetics
12.3 Pharmacokinetics Distribution In an in vitro human plasma study, iodixanol did not bind to protein. The volume of distribution in adults was 0.26 L/kg body weight, consistent with distribution to extracellular space. Elimination In 40 healthy, young male volunteers receiving a single intravenous administration of iodixanol in doses of 0.3 gram Iodine/kg to 1.2 gram Iodine/kg body weight, the elimination half-life was 2.1 hr. (± 0.1). Renal clearance was 110 ± 14 mL/min, equivalent to glomerular filtration (108 mL/min). These values were independent of the dose administered. Metabolism Iodixanol does not undergo metabolism. Excretion In adults, approximately 97% of the injected dose of iodixanol is excreted unchanged in urine within 24 hours, with less than 2% excreted in feces within five days post-injection. Specific Populations Pediatric: Forty pediatric patients ≤12 years old, with renal function that is normal for their age, received multiple intra-arterial administrations of iodixanol in doses of 0.32 gram Iodine/kg to 3.2 gram Iodine/kg body weight. The elimination half-lives for these patients are shown in Table 5. Dose adjustments to account for differences in elimination half-life in pediatric patients less than 6 months of age have not been studied. TABLE 5 MEAN ELIMINATION HALF-LIFE* IN PEDIATRIC PATIENTS Age Range Number of Patients Elimination half-life (hr. ± SD) Newborn to < 2 months 8 4.1 ± 1.4 2 to 6 months 8 2.8 ± 0.6 6 to 12 months 9 2.4 ± 0.4 1 to 2 y