高乌甲素磷脂复合物及其固体分散体在大鼠体内的药动学  

Pharmacokinetics of Lappaconitine-phospholipid Complex and Its Solid Dispersion in SD Rats in Vivo

作　　者：刘蒸生 郝海军[2] 马进安[1] LIU Zhengsheng;HAO Haijun;HAO Haijun(Department of Oncology,the Second Xiangya Hospital of Central South University,Changsha 410005,China;Shanghai Institute of Pharmaceutical Industry,Shanghai 201203,China)

机构地区：[1]中南大学湘雅二医院肿瘤科,长沙410005 [2]上海医药工业研究院,上海201203

出　　处：《医药导报》2018年第4期449-452,共4页Herald of Medicine

摘　　要：目的比较高乌甲素磷脂复合物及其固体分散体在SD大鼠体内的生物利用度。方法采用溶剂挥发法制备高乌甲素磷脂复合物及其固体分散体,X线衍射(XRD)法分析高乌甲素在磷脂复合物及其固体分散体的存在状态。SD大鼠分别灌胃给予高乌甲素原料药、磷脂复合物及磷脂复合物固体分散体(按高乌甲素计:5 mg·kg^(-1)),取血,以延胡索乙素为内标,高效液相色谱(HPLC)法测定血高乌甲素浓度,并计算主要药动学参数。结果高乌甲素磷脂复合物及其固体分散体的AUC_(0～t)与原料药相比都有显著性提高,其中磷脂复合物的AUC_(0～t)提高了1.41倍;固体分散体的AUC_(0～t)提高了2.04倍,且C_(max)显著提高。结论高乌甲素磷脂复合物及其固体分散体均可提高高乌甲素的口服生物利用度,且但高乌甲素磷脂复合物固体分散体效果更优。Objective To compare the relative bioavailability of lappaconitine phospholipids complex and itssolid dispersion.Methods Solvent evaporation method was employed to preparelappaconitine phospholipids complex and its solid dispersion,and their existential state was analyzed by X-ray diffraction(XRD).After each of groups of SD rats were administered intragastrically with lappaconitine,phospholipid complex,and its solid dispersion,respectively(equivalent to 5 mg·kg-1 of lappaconitine).The blood samples were collected at different time intervals.The concentration of lappaconitine in blood was analyzed by HPLC method using tetrahydropalmatine as internal standard,and then the main pharmacokinetic parameters were calculated.Results The AUC 0～t of the phospholipids complex and its solid dispersions were significantly increased as compared with that of lappaconitine.The AUC 0～t of phospholipid complex and its solid dispersion were increased by 1.41 and 2.04 times as compared to lappaconitine suspension,respectively.Conclusion The phospholipids complex and its solid dispersion could enhance the oral bioavailability of lappaconitine in SD rates notably.However,the bioavailability of lappaconitine phospholipids complexsolid dispersion is greater than that of phospholipids complex.

关 键 词：高乌甲素 磷脂复合物 固体分散体 生物利用度 

分 类 号：R286[医药卫生—中药学] R969.1[医药卫生—中医学]