title: 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.
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D002339:Carotid Arteries; D005260:Female; D007269:Injections, Intra-Arterial; D008353:Mannitol / Q000008:administration & dosage / Q000627:therapeutic use*; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000378:metabolism; D009994:Osmolar Concentration; D010592:Pharmaceutic Aids; D051381:Rats
chemical_list: D010592:Pharmaceutic Aids; D008353:Mannitol; D008727:Methotrexate