Distribution of therapeutic agents into the central nervous system following intranasal delivery

he enhanced cerebrospinal fluid (CSF) bioavailability reported for certain therapeutic agents following intranasal delivery suggests that drug administration via the nasal cavity may circumvent the blood brain barrier and allow direct central nervous system (CNS) targeting. In an attempt to identify structural characteristics which allow molecules to utilize the transport pathways accessible from the intranasal cavity to the CNS, disposition patterns of antihistamines and local anesthetics following nasal delivery were studied in rats. The CNS bioavailability following intranasal drug administration was assessed using either direct CSF sampling or microdialysis.;Intranasal delivery of antihistamines resulted in poor systemic bioavailabilities. Of the compounds studied, hydroxyzine achieved higher CSF concentrations after intranasal administration as compared to after the intra-arterial administration of an equivalent dose. Its CSF concentration after intranasal administration were seemingly independent of the plasma concentrations. In contrast, there were no differences in the CSF or plasma levels of triprolidine regardless of administration site. Chlorcyclizine and chlorpheniramine could be detected only in the plasma but not in the CSF.;Good bioavailability of the local anesthetics was observed in both the blood and CSF following intranasal administration. Plasma levels achieved after intranasal administration were found to be comparable to those measured after the intra-arterial administration of an equivalent dose, except in the case of procaine. The ratios of AUC;Disposition patterns measured using a direct CSF sampling technique were in good agreement with those found using a microdialysis technique. Following intranasal and intra-arterial administration of lidocaine, the rank order of the ratios of...