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

Objective: To support the clinical use of gadobenate dimeglumine for inject ion 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 a ssessments were carried out in rodents and non-rodents. Results: Initial adverse clinical signs in monkeys were associated with a s ystemic exposure 34 times higher than that found in humans after 0.1 mmol/k g 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 time s the human dose. Mutagenicity tests excluded any genotoxic potential of ga dobenate dimeglumine. Conclusion: Based on the wide margins of safety demonstrated in different s pecies, particularly in primates, gadobenate dimeglumine can be considered as safe in the range of clinical doses recommended for magnetic resonance i maging.