Modification of the blood-brain barrier permeability following intracarotid infusion of vinorelbine.

The effects of the antineoplastic compound, vinorelbine, on the permeability of the blood-brain barrier (BBB) to the complex Evans blue/albumin were studied. Vinorelbine, at a dose range from 5 to 10 mg/kg, was infused (4 ml/kg over 2 min) into the left carotid artery of anesthetised male Sprague-Dawley rats. BBB disruption was evaluated, qualitatively, by the appearance in the infused hemisphere of intravenously administered Evans blue dye (2%). Six groups of 3 rats were studied for preliminary assays to define the dose and delay between infusion and sacrifice. Twenty four rats (12 controls and 12 test rats) were used to define the effect of vinorelbine. These effects of vinorelbine were dose dependent and after 3 hours, 10 mg/kg of vinorelbine caused Evans blue/albumin exudation in gray and white matter. This study shows that the intracarotid infusion of vinorelbine in this rat model system increases BBB permeability only with a high dose. Sufficient concentrations of drug may be obtained in cerebral tissue without significant BBB disruption.