Modification of the blood-brain barrier permeability by vinorelbine: effect of intracarotid infusion compared with intravenous infusion

Abstract

Brain levels of the antineoplastic compound, vinorelbine, and its effects on the permeability of the blood-brain barrier (BBB) were studied. Preliminary experiments were carried out to define the dose of 10 mg/kg and the delay of 3 h after infusion required to induce BBB disruption. Vinorelbine was infused by i.c. or i.v. infusion to anesthetized male Sprague-Dawley rats. BBB disruption was evaluated qualitatively by the presence in the infused hemisphere of i.v. administered Evans blue dye (2%) and vinorelbine intratissular levels were measured by HPLC. After an i.c. infusion, there is an important variability in the degree of extravasation of Evans blue albumin complex, which is correlated with vinorelbine levels (p < 0.01). The percent of dose in brain tissue is less than 1%. After an i.v. infusion, the parenchyma is globally affected as shown by the uniform faint bluish staining of the two hemispheres. Vinorelbine levels are homogenous and similar to levels of brains graded + 1 after an i.c. infusion. These results seem to indicate that an i.c. infusion induces localized BBB disruptions while the effect of an i.v. infusion is global and that the gain in tissue level after an i.c. infusion is low compared with i.v. infusion.