indication

Gadofosveset trisodium is used as a contrast agent in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease.

pharmacology

In human studies, gadofosveset substantially shortened blood T1 values for up to 4 hours after intravenous bolus injection. Relaxivity in plasma was measured to be 33.4 to 45.7 mM^-1s^-1 (0.47 T) over the dose range of up to 0.05 mmol/kg.

mechanism of action

Gadofosveset binds reversibly to endogenous serum albumin resulting in longer vascular residence time than non-protein binding contrast agents. The binding to serum albumin also increases the magnetic resonance relaxivity of gadofosveset and decreases the relaxation time (Tl) of water protons resulting in an increase in signal intensity (brightness) of blood.

toxicity

Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/min/1.73m²).

biotransformation

Gadofosveset does not undergo measurable metabolism.

half life

The mean half-life of the distribution phase is 0.48 ± 0.11 hours and the mean half-life of the elimination phase is 16.3 ± 2.6 hours.

route of elimination

Gadofosveset is eliminated primarily in the urine with approximately 83.5% of an injected dose excreted in the urine over 14 days. Ninety-four percent (94%) of urinary excretion occurs in the first 72 hours. A small portion of gadofosveset dose is recovered in feces (approximately 4.7%).

drug interactions

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.