Preclinical safety evaluation of Gd-EOB-DTPA (Primovist).

Objectives: Gadoxetic acid [gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA); Primovist] is a liver specific contrast agent for magnetic resonance imaging. For risk assessment of the single diagnostic use the toxicity of this compound was assessed.

Materials And Methods: Studies into acute, repeated-dose, reproductive and developmental toxicity, and local tolerance, contact sensitizing, and genotoxic potential were performed.

Results: Lethality was observed after a single intravenous administration at doses 2 orders of magnitude higher than the clinical dose. The no observed adverse effect levels after repeated administration markedly exceeds the single diagnostic dose in humans and no unexpected organ toxicity was observed. No indications of reproductive and developmental toxicity, potential contact allergenic, and genotoxic effects were observed. Gd-EOB-DTPA was well tolerated after intravenous administration.

Conclusions: Gd-EOB-DTPA was well tolerated with high safety margins between the single diagnostic dose and the doses showing adverse effects in animal studies.