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.
Wang
Qiao
Q
Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, PR China. wangqiao-1@163.com
Chen
Guoshen
G
D000281:Administration, Intranasal; D000470:Alkaloids; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D007262:Infusions, Intravenous; D008297:Male; D013058:Mass Spectrometry; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000470:Alkaloids; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C050426:huperzine A