Effect of osmotic blood-brain barrier disruption on methotrexate pharmacokinetics in the dog

Infusion of 25% mannitol into the internal carotid artery of the dog results in a reversible disruption of the blood-brain barrier (BBB). This osmotic BBB disruption enhances the penetratin of systemically administered methotrexate (MTX) into the ipsilateral cerebral hemisphere. Brain methotexate levels were maximized by giving this chemotherapeutic drug by the intracarotid rather than the intravenous route after osmotic BBB disruption. Assays of MTX levels in cerebrospinal fluid were found to be a very unreliable and inconsistent monitor of brain MTX levels after osmotic BBB disruption.