Abstract
Nasal transport of thymidine (Thd) was investigated using in vivo nasal absorption technique in rats. Radio active thymidine was administered and Thd concentrations in the cerebrospinal fluid (CSF) and plasma was determined by liquid scintillation counter. Thd concentrations in the fractionated CSF which located close to the nasal cavity following intranasal (i.n.) administration were higher than that following intravenous (i.v.) administration, thus these observation suggests Thd, like other compounds, transported from nasal cavity to CSF directly following i.n. administration. The fractionated CSF concentration and the area under plasma concentration-time curve (AUC) following i.n. administration of Thd at 1.338∼267.6 mM were determined. The relationships between both the fractionated CSF concentration and AUC, and dose of Thd seemed dose-independent, though saturation in the transport of Thd from nasal membrane to CSF and systemic circulation was observed. The CSF concentrations and AUC following i.n. administration of Thd at a dose of 13.38 mM with 2'-deoxyuridine (dUrd, 25, 50 and 100 mM) or 2'-deoxyinosine (dIno, 50 mM) were also determined. Decrease in the concentration of CSF and AUC was observed, and the inhibitory effect of dUrd was dose-dependent. In the case of coadministration of Thd and dIno, dIno also showed an inhibitory effect for Thd transport, while the effect was less significant than that of dUrd. These results suggests that the possibility of the presence of Thd sensitive transport systems on nasal membrane in rats, and the systems, if exist, may be useful for the delivery of nucleoside analogues for central nervous system and systemic circulation via nasal membrane.
