Enhancement of CNS penetration of methotrexate by hyperosmolar intracarotid mannitol or carcinomatous meningitis

Abstract

Intracarotid (i.c.) hyperosmolar mannitol enhances central nervous system (CNS) penetration of intravenous (i.v.) methotrexate (MTX) in normal adult rats. A fivefold augmentation in the CSF:serum and ipsilateral brain:serum MTX concentration ratios was observed 1 hour after drug administration. Intravenous mannitol had no such effect. Rats with meningeal carcinomatosis have a partial defect in blood-brain barrier function, and the CSF:serum MTX concentration ratio was 4.6 times higher in these animals than in normal rats prior to mannitol therapy. Intracarotid hyperosmolar mannitol further augmented the blood-brain barrier permeability to intravenous MTX. Intracarotid mannitol increased the therapeutic effect of MTX, since rats with meningeal carcinomatosis that received i.v. MTX and i.c. mannitol experienced a slight enhancement in survival.