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The objective of the present study was to clarify the relation between drug transport to the cerebrospinal fluid (CSF) from the nasal cavity and the lipophilicity of the drug using hydrophilic sulfonamides as model drugs. The nasal cavity of the rat was perfused in a single pass system and the concentrations of sulfonamides in plasma and CSF were measured. The drug concentrations in CSF and plasma after nasal perfusion were compared with those after intravenous (i.v.) administration. The drug concentrations in the CSF were remarkably high after nasal perfusion in comparison with those after i.v. administration, though the time course of the plasma concentration was not much different from that after i.v. administration. These results suggested the existence of a direct transport pathway of the sulfonamides from the nose to the CSF. In addition, the drug concentrations in the CSF increased with increasing the lipophilicity of the drugs (the partition coefficient (Pc) of the drugs between isoamyl alcohol and pH 7.4 phosphate buffer). A significant correlation was observed between the drug concentrations in CSF and Pc. In conclusion, the direct transport pathway of the sulfonamides from the nose to the CSF was confirmed and, with regard to drugs with comparatively low lipophilicity, the degree of the transport depended on its Pc.

The Transport of a Drug to the Cerebrospinal Fluid Directly from the Nasal Cavity: The Relation to the Lipophilicity of the Drug.