Transnasal delivery of 5-fluorouracil to the brain in the rat.
The purpose of this research is to clarify the feasibility and to determine the extent of transnasal drug delivery to the brain through the cerebrospinal fluid (CSF) in the rat, using 3H-5-fluorouracil (5FU) as a model drug. It was confirmed first that the concentration of 5FU in the CSF was significantly higher following nasal administration compared with intravenous injection, indicating direct transport of 5FU from the nasal cavity to the CSF. Concentration-time profiles of 5FU in the plasma and in the cerebral cortex were determined following intravenous infusion, nasal instillation and nasal perfusion. In order to evaluate the extent of drug transport from the nasal cavity to the cerebral cortex by way of the CSF, the apparent brain uptake clearances were calculated. The uptake clearance following nasal perfusion (8.65 microl/min/g tissue) was significantly large (p < 0.001) in comparison with that following intravenous infusion (6.20 microl/min/g tissue), while that following nasal instillation (6.94 microl/min/g tissue) was not. Consequently, significant amount of 5FU is transported from the nasal cavity to the brain through the CSF and thus, the delivery of the hydrophilic drug to the brain is augmented by nasal drug application.
Sakane
T
T
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan. sakane@pharm.setsunan.ac.jp
Yamashita
S
S
Yata
N
N
Sezaki
H
H
D000281:Administration, Intranasal; D000465:Algorithms; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D009296:Nasal Cavity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil