Intracarotid infusion of hypertonic mannitol changes permeability of blood-brain barrier to methotrexate in rats.
OBJECTIVE
To study whether infusion of hypertonic mannitol through internal carotid artery could enhance methotrexate (MTX) concentration in rat cortex and to study the time-course of this process.


METHODS
Hypertonic mannitol was infused into the rat left internal carotid artery, ten minutes later, MTX was injected from the left femoral vein (i.v.) or left common carotid artery (ia), and the concentration of MTX was assayed 1 h later. Rats were given MTX at different time interval after infusion of mannitol, and the concentration of MTX was assayed 1 h after drug administration. At the same time, the rat cortex's density was analyzed.


RESULTS
After mannitol infusion, MTX's concentration in rat cortex increased 2.54 times (i.v.) and 3.41 times (ia) as compared to control, respectively. After 10 min, such effect reached its peak, and almost disappeared after 6 h. There was no significant change in rat cortex's density.


CONCLUSIONS
Mannitol can make blood-brain barrier (BBB) reversibly permeable, and increase MTX concentration in brain without any obvious injury to the brain.
Pan
G Y
GY
Center of Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. panguoyu@hotmail.com
Liu
X D
XD
Liu
G Q
GQ
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002343:Carotid Artery, Internal; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006982:Hypertonic Solutions; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D008353:Mannitol / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006982:Hypertonic Solutions; D008353:Mannitol; D008727:Methotrexate