Omniscan Mechanism of Action

Pharmacology: Pharmacodynamics: The paramagnetic properties of OMNISCAN provides contrast enhancement during MRI.
There were no clinically significant deviations from pre-injection values in haemodynamic and blood and urine laboratory parameters following intravenous injection of gadodiamide in healthy volunteers. However, a minor transient change in serum iron levels 8 to 48 hours after gadodiamide injection was observed.
Pharmacokinetics: Distribution: Gadodiamide is rapidly distributed in the extracellular fluid. The volume of distribution is equivalent to that of extracellular water. The distribution half-life is approximately 4 minutes and the elimination half-life is approximately 70 minutes.
Elimination: Gadodiamide is excreted through the kidneys by glomerular filtration. In patients with normal renal function approximately 85% of the administered dose is recovered in the urine by 4 hours and 95-98% by 24 hours after intravenous injection. The renal and total clearance rates of gadodiamide are nearly identical, and are similar to that of substances excreted primarily by glomerular filtration.
The elimination half-life of OMNISCAN is prolonged in patients with impaired renal function. No dose dependent kinetics have been observed after injection of 0.1 and 0.3 mmol/kg.
No metabolites have been detected. No protein binding has been observed.
Following GBCA administration, trace amounts of gadolinium is present for months or years in brain, bone, skin, and other organs.
Toxicology: Preclinical safety data: In vitro studies have demonstrated no or insignificant effects on mast cell histamine release, human serum complement activation factors, human erythrocyte cholinesterase activity, lysozyme activity, human erythrocyte fragility and morphology, and on tension in isolated bovine blood vessels. No evidence of antigenicity was seen in a dermal test in Guinea pigs. OMNISCAN had no effects on fertility or reproductive performance in rats or in teratology studies in rats and rabbits at doses that did not cause maternal toxicity.
Studies conducted in healthy rats injected repeatedly with GBCAs demonstrated progressive and persistent T1-weighted hyperintensity on MRI in the deep cerebellar nuclei (DCN) that was higher with linear than with macrocyclic agents. Signal enhancement in the globus pallidus (GP) could not be seen in the animals.
GBCA administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one-month postnatal age.
Quantitative results using mass spectrometry demonstrated that the total gadolinium concentrations were significantly higher following repeated administration of the linear GBCAs than following macrocyclic GBCAs. These studies reported no abnormal behavioural changes suggestive of neurological toxicity.