天麻素经十二指肠给药后的大鼠脑药动学特征（英文）

Neuropharmacokinetics of gastrodin in rat brain after intraduodenal administration

目的研究天麻素在大鼠十二指肠给药后的脑药动学和不同脑区的分布。方法将大鼠麻醉后,通过其十二指肠给天麻素,剂量为200 mg·kg^(-1)。在规定时间点收集血浆、脑脊液和4个不同脑区(皮质、海马、丘脑、小脑)的脑微透析液。采用HPLC法测定所收集液体中的药物浓度,采用DAS 2.0药动学软件计算药动学参数。结果天麻素给药后能迅速进入脑部,4个不同脑区和脑脊液的t_(max)分别为(40.0±6.1)、(42.5±7.7)、(37.5±9.5)、(42.5±7.7)和(55.8±16.0)min,其AUC与血浆AUC的比值分别为(2.6±1.0)%、(2.6±0.9)%、(3.0±0.9)%、(5.3±2.1)%和(6.0±2.6)%。天麻素在小脑的AUC明显大于在其他3个脑区的AUC(P<0.05)。结论天麻素经十二指肠给药后能迅速入脑部,但是入脑量低,所有AUC_脑/AUC_(血浆)均<6%。

AIM To study the neurophannacokinetics and brain distribution of gastrodin after intraduodenal ad- ministration in rats. METHODS Gastrodin was administered via duodenum at 200 mg-kg-1 and blood plasma, cere- brospinal fluid （CSF） and brain microdialysate （frontal cortex, hippocampus, thalamus and cerebellum） were collected at the indicated time intervals for the measurement of gastredin concentrations by high performance liquid chromatogra- phy. The pharmacokinetic parameters were calculated by non-compartmental analysis using DAS 2.0 software. RESULTS Gastmdin can be transported to brain and quickly access to brain tissues after intraduodenal administration. The tmax in brain （ frontal cortex, hippocampus, thalamus and cerebellum） and in CSF were （40.0 ± 6.1）, （42.5 ± 7.7）, （37.5± 9.5）, （42.5±7.7） and （55.8 ± 16.0）min, respectively. The ratios of AUC in frontal cortex, hippocampus, thala- mus, cerebellum and CSF to AUC in plasma were （2.6±1.0）%, （2.6±0.9） %, （3.0±0.9） %, （5.3±2.1）% and （6.0±2.6）%, respectively. AUC in cerebellum was significantly higher than that in other regions （ P 〈 0.05）. CONCLUSION Gastrodin can be transported to brain and quickly access to brain tissues after intraduodenal administration, although the amount of gastrodin in brain is low and all of AUCbrain/AUCplasma are less than 6%.