BRAIN PENETRATION AND NEUROLOGICAL EFFECTS OF GADOBENATE DIMEGLUMINE IN THE RAT

Purpose: The study aimed at measuring the amount of the gadobenate ion that crosses an experimentally disrupted blood-brain barrier (BBB) in rats following i.v. administration of gadobenate dimeglumine (GD). Th e intention was also to compare this amount with the minimally effecti ve intrathecal dose that alters the cerebral function. Methods: Spragu e Dawley rats with an osmotically disrupted BBB received 0.3 mmol/kg o f (Gd-153)GD, i.v. Radioactivity was measured in plasma and brain pare nchyma. The effect on the cerebral function was evaluated by means of a standard motor coordination test (Rota-rod test). Results: Brain lev els of the gadobenate ion were approximately 60 nmol/g tissue after i. v. injection of GD. In rats with an intact BBB, the lowest dose of GD able to slightly impair motor coordination was 0.01 mmol/kg following intracisternal injection. Conclusion: I.v. administration of GD to rat s with a disrupted BBB results in brain levels of the gadobenate ion t hat are more than 20 times lower than those reached following intrathe cal administration of the minimal effective dose, as determined by the Rota-rod test.