Author(s): Wang F, Jiang X, Lu W
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Abstract The aim of this paper was to investigate the levels of methotrexate (MTX) in blood and the cerebrospinal fluid (CSF) in rats to find out whether there is any direct drug transport from nasal cavity to CSF following intranasal administration. Methotrexate was administered to male Sprague-Dawley rats either intranasally or intravenously. Drug concentrations were determined from CSF and plasma samples collected from the cisterna magna and caudal vein, respectively. To collect CSF sample continuously, blank artificial CSF was infused into the lateral ventricle. The plasma levels achieved following intranasal administration were significantly lower than those after intravenous administration (P<0.01) were, while CSF concentrations achieved after intranasal administration were significantly higher than those after intravenous administration (P<0.01). The ratio of the AUC(CSF) value between the intranasal route and the intravenous injection was 13.76, whereas the absolute bioavailability was only 6.3\%, the drug targeting index (DTI) of nasal route was 21.7. In conclusion, these results showed that the antineoplastic MTX must be directly transported from the nasal cavity into the CSF in rats.
This article was published in Int J Pharm
and referenced in Journal of Nanomedicine & Nanotechnology