Distribution and metabolism of gastrodin in rat brain.

Gastrodin is the major and bioactive component in Tianma (Gastrodia elata Bl.) and has sedative, anticonvulsive and neuroprotective effects. Since little is known about its neuropharmacokinetics and brain metabolism, this study was undertaken to investigate the kinetic inter-relationship of gastrodin in rat plasma, cerebrospinal fluid (CSF) and brain microdialysate (frontal cortex, hippocampus, thalamus and cerebellum). Gastrodin was administered via the femoral vein at a dose of 200mg/kg, and blood, CSF and brain microdialysate were collected at timed intervals for the measurement of gastrodin concentrations by high-performance liquid chromatography. The samples were analyzed on a Diamonsil C18 column (5 microm, 250 mm x 4.6mm i.d.) with a mobile phase consisting of acetonitrile-water (5% acetonitrile for brain microdialysate, 2.5% acetonitrile for plasma and CSF), and detected with a UV detector at 221 nm. The distribution of gastrodin in rat showed that levels of gastrodin declined rapidly after drug administration, and the entry of gastrodin into the brain was rapid. However, the ratios of AUC(brain)/AUC(plasma) were not high. The individual ratios of the AUC in the CSF, frontal cortex, hippocampus, thalamus and cerebellum to the AUC in the plasma were 4.8+/-2.4%, 3.3+/-1.2%, 3.0+/-0.7%, 3.3+/-1.3% and 6.1+/-1.9%, respectively. The AUC in the cerebellum was significantly higher than that in other brain regions (P<0.05). The concentrations of p-hydroxybenzyl alcohol, the main metabolite of gastrodin, were very low both in the CSF and plasma.

Pharmacokinetics of Gastrodin in rat plasma and CSF after i.n. and i.v.

The pharmacokinetic behavior of Gastrodin in rat plasma and cerebrospinal fluid (CSF) after intranasal and intravenous administration (50mg kg(-1)) was investigated. Intranasal administration of Gastrodin provided a comparable AUC in CSF compared with the intravenous administration. But Gastrodin level in plasma was very low. The ratios of AUC values of intranasal to intravenous administration were 8.85% and 105.5% in plasma and CSF, respectively. The drug targeting index (DTI) was 12.34. In conclusion, intranasal administration of Gastrodin is a promising alternative to traditional administration. Olfactory mucosa did present another pathway for transport Gastrodin to the brain.