Toxicological safety evaluation of gadobenate dimeglumine 0.5 M solution for injection (MultiHance), a new magnetic resonance imaging contrast medium.

Objective: To support the clinical use of gadobenate dimeglumine for injection as an intravascular magnetic resonance imaging contrast medium through an extensive battery of toxicological safety studies.

Methods: Single and multiple dose toxicity, reproduction and mutagenicity assessments were carried out in rodents and non-rodents.

Results: Initial adverse clinical signs in monkeys were associated with a systemic exposure 34 times higher than that found in humans after 0.1 mmol/kg gadobenate dimeglumine. Good systemic tolerance was observed in repeated dose toxicity studies. Reproductive performance and physical and behavioral development of offspring were unaffected at doses corresponding to 20 times the human dose. Mutagenicity tests excluded any genotoxic potential of gadobenate dimeglumine.

Conclusion: Based on the wide margins of safety demonstrated in different species, particularly in primates, gadobenate dimeglumine can be considered as safe in the range of clinical doses recommended for magnetic resonance imaging.