Pharmacokinetic behavior of huperzine A in plasma and cerebrospinal fluid after intranasal administration in rats

The aim of this study was to investigate the pharmacokinetic behavior of huperzine A (Hup A) in plasma and cerebrospinal fluid (CSF) after intranasal administration (0.5 mg/kg) in male Sprague‐Dawley rats. A pharmacokinetic study of intravenous Hup A (0.5 mg/kg) was also performed. The concentrations of Hup A in the biological samples were measured by high performance liquid chromatography–mass spectrometry. Blood samples were taken from the tail vein and CSF was sampled by cisternal puncture using a stereotaxic frame. The contribution of the olfactory pathway to the uptake of Hup A into CSF was determined by comparing the AUC_CSF/AUC_plasma ratios after intranasal and intravenous administration. The AUC ratios of intranasal to intravenous administration in CSF and plasma were 104% and 118%, respectively. No significant difference was observed between the AUC_CSF/AUC_plasma ratios of Hup A after intranasal administration (20%) and after intravenous infusion (23%). This indicated that approximately 20% of the Hup A level in plasma reached the CSF after both nasal and intravenous administration, and that no direct transport of Hup A from nose to CSF was found in rats. Copyright © 2009 John Wiley & Sons, Ltd.