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

• Published in: Journal of computer assisted tomography Vol. 23 Suppl 1; p. S195
• Main Authors: Tirone, P, Castano, M, Cipolla, P, Frigeni, V, La Noce, A, Luzzani, F, Valenti, R, de Haën, C
• Format: Journal Article
• Language: English
• Published: United States 01.11.1999
• Subjects: Animals; Blood-Brain Barrier - drug effects; Contrast Media - administration & dosage; Contrast Media - pharmacology; Drug Hypersensitivity - etiology; Gadolinium - administration & dosage; Gadolinium - pharmacology; Guinea Pigs; Heart - drug effects; Hemodynamics - drug effects; Injections, Intravenous; Kidney - drug effects; Liver - drug effects; Lung - drug effects; Magnetic Resonance Imaging; Male; Meglumine - administration & dosage; Meglumine - analogs & derivatives; Meglumine - pharmacology; Mononuclear Phagocyte System - drug effects; Myocardial Ischemia - drug therapy; Organometallic Compounds - administration & dosage; Organometallic Compounds - pharmacology; Rats; Rats, Sprague-Dawley; Swine; Swine, Miniature
• ISSN: 0363-8715; 1532-3145
• DOI: 10.1097/00004728-199911001-00024

To assess in animals the pharmacological tolerability for intravascular gadobenate dimeglumine. 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. 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.