Evaluation of brain-targeting for the nasal delivery of ergoloid mesylate by the microdialysis method in rats

The aim of this study was to quantify the nasal delivery of ergoloid mesylate (EM) to the brain by comparing cerebrospinal fluid (CSF) and plasma EM levels after nasal administration at a dose of 4 mg/kg with those after intravenous administration. Following nasal delivery, EM reached a C-a value (mean +/- SD) in plasma of 348.41 +/- 19.47 ng/ml and in CSF of 87.35 +/- 6.37 ng/ml after 107 and 20 min, respectively, while after intravenous injection, EM reached a C-max value (mean +/- S.D.) in CSF of 54.81 +/- 4.92 ng/ml at 60 min and the C-max in plasma was 1255.51 +/- 133.59 ng/ml. The AUC(CSF)/AUC(plasma) ratio (0.48 +/- 0.05) after intranasal delivery differed greatly from the ratio (0.14 +/- 0.04) observed after intravenous injection (P < 0.05). The further analyzed data demonstrated a statistically significant distribution advantage of EM to the brain via the nasal route, and further suggesting that nasal administration can be a promising alternative for EM that undergoes first-pass metabolism following oral administration. (C) 2007 Elsevier B.V. All rights reserved.