General pharmacology in experimental animals of gadobenate dimeglumine (MultiHance), a new magnetic resonance imaging contrast agent.
OBJECTIVE
To assess in animals the pharmacological tolerability for intravascular gadobenate dimeglumine.


RESULTS
Cardiovascular effects: In healthy animals no relevant effects were observed apart from slight and transient increases in cardiac output and decreases in systemic vascular resistance. In pigs with myocardial ischemia: doses up to 3.0 mmol/kg caused dose-dependent decreases in heart rate, systemic vascular resistance and mean arterial blood pressure along with transient increases in cardiac output. In vitro: Myocardial contractility was slightly depressed after direct exposure to a 30 mM solution. Respiratory effects in healthy pigs: no effects after 1.0 mmol/kg i.v. Effects on the central nervous system: In healthy animals: gadobenate dimeglumine, 1.0 mmol/kg i.v, did not penetrate nor impair the blood-brain barrier in rats and did not affect behavior, motor coordination or EEG. In pathological models: even in the presence of an osmotically disrupted blood-brain barrier, brain penetration of gadobenate was poor and no signs of epileptogenic potential were evident. Effects on blood: No hemolytic potential was observed. Plasma coagulation was slightly affected in vitro but not in vivo. Effects on kidney and liver function: Transient increases in diuresis, without effects on blood and urine enzymes were observed at doses of 1.25 and 2.5 mmol/kg.


CONCLUSIONS
The clinical use of gadobenate dimeglumine as an intravascular magnetic resonance imaging contrast agent is strongly supported by the good tolerability of the product in healthy and pathological animal models.
Tirone
P
P
Milano Research Centre, Bracco SpA, Milan, Italy.
Castano
M
M
Cipolla
P
P
Frigeni
V
V
La Noce
A
A
Luzzani
F
F
Valenti
R
R
de Haën
C
C
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000494:pharmacology*; D004342:Drug Hypersensitivity / Q000209:etiology; D005682:Gadolinium / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013556:Swine, Miniature
D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium