摘要
目的探讨剂量因素及冰片对阿魏酸钠在小鼠血浆和脑区中药动学的影响。方法经ig给予小鼠单用高、低剂量阿魏酸钠或复合不同剂量冰片的低剂量阿魏酸钠,采用HPLC法测定高剂量阿魏酸钠在达峰时间及低剂量阿魏酸钠在不同时间点的血浆和脑区中药物浓度,采用PCNONLIN程序计算药动学参数。结果单给阿魏酸钠低剂量组。其t_(max)为5.0 min,C_(max)为44.1μg/mL,AUC_(0～30)为853.9μg/(mL·min);脑区中海马AUC_(0～30)为11.8μg/(g·min),t_(max)为5.0 min.C_(max)为1.4μg/g;阿魏酸钠高剂量组与低剂量组比较.血药浓度仅增加2.5倍;脑区中浓度增加最多的小脑也仅增加1.9倍。其中海马没有增加;联用冰片后.冰片能加快阿魏酸钠在海马的分布,并显著提高其在海马中的量。阿魏酸钠200 mg/kg联用冰片50 mg/kg,海马C_(max)与AUC_(0～30)分别增加1.2倍和1.7倍。结论单纯加大阿魏酸钠的给药剂量不能相应提高其在脑中的浓度,联用冰片可提高其脑内(特别是海马)的生物利用度,阿魏酸钠联用冰片在治疗脑缺血等中枢神经系统疾病中可能有显著的临床意义。
Objective To explore the pharmacokinetics of dosage factor and borneol on sodium ferulic （SF） in plasma and in brain regions of mice. Methods Mice were treated with SF （ig） alone or accompanied by borneol in different doses, the sample from plasma and different brain regions were obtained at different time points （2.5, 5, 7.5, 10, 15, and 30 min）, respectively after application of SF. HPLC was employed to determine the concentrations of SF in plasma and in brain regions of mice. Pharmacokinetic parameters were assayed by using PCNONLIN software. Results AUC0-30, tmax, and Cmax of single low dose SF （0.2 g/kg） in plasma were 853.9μg/（mL·min）, 5.0 min, and 44.1 μg/mL, respectively and that in hippocampus were 11.8μg/（g·min）, 5.0 min, and 1.4 μg/g, respectively; Single high close SF （2 g/kg, ig） could only increase 2.5 times in plasma and 1.9 times in cerebellar region compared to single low dose SF （0.2 g/kg, ig）. No changes was found in hippocampus. Borneol （50 mg/kg） not only accelerated the distribution of SF in hippocampus （tmax in advance 2.5 min）, but also increased the concentration of that in plasma. Compared to single low dose SF （0.2 g/kg） group, the Cmax and AUC0-30 are increased to 1. 2 times and 1.7 times, respectively in hippocampus in single low dose SF （0.2 g/kg） plus borneol （50 mg/ kg） group. Conclusion Increasing the dose of SF alone dose not increase the concentration of SF appropriately in brain. The concentration of SF in plasma and that in brain regions are increased by borneol. Totally, these results suggest that the application of SF combined with borneol for CNS diseases, such as brain ischemia, might be more effective in clinic.
出处
《中草药》
CAS
CSCD
北大核心
2008年第4期551-556,共6页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金(30400547)
广东省自然科学基金(04300310)
关键词
冰片
阿魏酸钠
高效液相色谱
血药浓度
脑区
borneol
sodium ferulate （SF）
HPLC
blood concentration
brain region
