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.


CONCLUSIONS
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.
Morisetti
A
A
Milan Research Centre of Bracco SpA, Italy.
Bussi
S
S
Tirone
P
P
de Haën
C
C
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics; D012449:Safety
D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium