基于西伯利亚远志糖A5、A6体内表征的开心散与远志及单体药代动力学关联分析

目的在记忆障碍模型大鼠下,对比分析单体(西伯利亚远志糖A5和西伯利亚远志糖A6)、单味药(远志)和复方(开心散)3个层次的药动学特性及其相互作用性(PK-DI),考量远志与复方在治疗痴呆中的药物属性。方法采用HPLC-PDA同时测定给药后记忆障碍模型大鼠体内西伯利亚远志糖A5和西伯利亚远志糖A6血药浓度,获得各药物体内药代动力学表征数据,kinetics4.4软件处理数据。采用PK-DI关联分析法对比分析不同药物形式的特性表征。结果西伯利亚远志糖A5和西伯利亚远志糖A6药-时曲线均使用非房室模型处理。远志和开心散药代动力学表征相似,均呈现双峰吸收,而西伯利亚远志糖A5和西伯利亚远志糖A6单体药代动力学表征发生明显改变,呈单峰吸收。西伯利亚远志糖A5和西伯利亚远志糖A6的AUC值在远志组和开心散组间无明显差异,均远远大于单体组(P0.01)。而与单味药远志相比,开心散复方药物状态下的最大血药浓度大幅增加(P0.05)。结论与单体相比,单味药远志和开心散复方的药代动力学表征发生了改变,生物利用度大幅提高,且复方配伍后更是增大了药物作用强度,表征出复方药物协同作用特性,从而展示出了复方具有其药物属性特性。

Correlation analysis between pharmacokinetics of Kaixin San,Radix Po-lygalae and its monomer based on internal representations of sibiricose A5 and A6 in rats with acquired dysmnesia

Objective To study anti-dementia effects of Kaixin San ( Joyful Powder ) and Radix Polygalae's based on pharmacokinetic characteristics of sibiricose A5, sibiricose A6, 3,6'-disinapoyl sucrose, and polygala xanthone Ⅲ in rats with acquired dysmnesia model from three levels: monomer,medicinal and formula.Method Serum concentrations of sibiricose A5 and sibiricose A6 after oral administration in rat model were measured by using HPLC-PDA Pharmacokinetic data were obtained. Then different forms of sibiricose A5 and A6 were compared with correlation analysis ( PK-DI ) . Result Concentration-time curves showed that the pharmacokinetic profiles were similar in the absorption phase when Radix Polygalae extract and Kaixin San were orally administered.A bimodal patternof sibiricose A5 and A6 in the serum profile was revealed.However, this phenomenon was not observed in the group of monomer.Radix Polygalae extracts and Kaixin San were similar in the measurements of AUC, and levels of monomer were decreased significantly (P<0.01).Compared to the oral administration of Radix Polygalae extract, Cmax-1 and Cmax-2 of Kaixin San were increased significantly ( P<0.05) .Conclution The results showed that the absorption of sibiricose A5 and A6 in rats was superior when Kaixin San was administered.This finding supports the rationale for using the Kaixin San combination in clinical use.