General pharmacology in experimental animals of gadobenate dimeglumine (MultiHance), a new magnetic resonance imaging contrast agent.

摘要

OBJECTIVES: 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.