Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, PR China.
Biopharm Drug Dispos. 2009 Dec;30(9):551-5. doi: 10.1002/bdd.686.
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.
本研究旨在研究雄性 Sprague-Dawley 大鼠经鼻腔给药（0.5mg/kg）后，其血浆和脑脊液（CSF）中石杉碱甲（Hup A）的药代动力学行为。还进行了静脉内 Hup A（0.5mg/kg）的药代动力学研究。采用高效液相色谱-质谱法测定生物样品中 Hup A 的浓度。通过立体定位框架从尾静脉采集血样，并通过脑池穿刺采集 CSF。通过比较鼻腔和静脉给药后 CSF 和血浆中的 AUC（CSF）/AUC（血浆）比值，确定嗅觉途径对 Hup A 进入 CSF 的摄取的贡献。鼻腔给药后 CSF 和血浆中的 AUC 比值分别为 104%和 118%。鼻腔给药后（20%）和静脉输注后（23%）Hup A 的 AUC（CSF）/AUC（血浆）比值无显著差异。这表明，鼻内和静脉内给药后，约 20%的 Hup A 水平到达 CSF，并且在大鼠中未发现 Hup A 从鼻子直接转运到 CSF。
