吴茱萸碱衍生物纳米粒体内药动学和生物等效性研究  

Pharmacokinetics and bioequivalence of evodiamine butyryl derivative-loaded lipid nanoparticles in rats

作　　者：杨兰 万坤 杨建波 晏声蕾 张奇娆 张景勍 胡雪原 YANG Lan;WAN Kun;YANG Jian-bol;YAN Sheng-lei;ZHANG Qi-rao;ZHANG Jing-qing;HU Xue-yuan(Medicine Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China;Meishan Cardio Cerebrovascular Disease Hospital, Meishan 620020, China)

机构地区：[1]重庆医科大学药学院重庆高校药物工程研究中心,重庆400016 [2]四川省眉山市心脑血管病医院,四川眉山620020

出　　处：《中草药》2018年第9期2114-2118,共5页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(30973645);重庆市研究生科研创新项目资助(CYS17172);重庆医科大学大学生科学研究与创新实验项目(201724)

摘　　要：目的研究吴茱萸碱丁酰基衍生物(evodiamine butyryl derivative,EAB)及其固体脂质纳米粒(evodiamine butyryl derivative-loaded lipid nanoparticles,EABLN)在大鼠体内的药动学行为并比较其生物等效性。方法采用薄膜超声法制备EABLN,将16只SD雄性大鼠随机分为2组,分别ig EAB或EABLN(100 mg/kg),并在给药后的各个时间点对大鼠进行眼眶后静脉丛取血,建立高效液相色谱方法测定EAB的血药浓度;用DAS软件分析各药动学数据并比较生物等效性。结果EABLN的主要药动学参数AUC0~72 h、Cmax和tmax分别为(11 535.39±261.08)μg·h/L、(886.73±15.40)μg/L和(2.00±0.17)h,EABLN的相对生物利用度为143%。EAB和EABLN的AUC0~72 h和Cmax生物等效性合格,但tmax生物等效性不合格。结论EABLN改善了EAB在大鼠体内的药动学行为,明显提高了EAB的口服生物利用度,且EABLN与EAB之间不具有生物等效性。Objective To study the pharmacokinetic characteristics and bioequivalence of evodiamine butyryl derivative（EAB） and evodiamine butyryl derivative-loaded lipid nanoparticles（EABLN） in rats. Methods EABLN were prepared by a film ultrasound method, 16 male SD rats were randomly divided into two groups, and their blood were extracted from eye socket after they were intragastric administrated EAB or EABLN（100 mg/kg） for a given time period. Plasma concentration of EAB was determined by HPLC, then pharmacokinetic data, bioequivalence between EAB and EABLN were analyzed by DAS software. Results The main pharmacokinetic parameters of EABLN were listed, AUC（0—72 h）, Cmax, and tmax were（11 535.39 ± 261.08） μg·h/L,（886.73 ± 15.40） μg/L, and（2.00 ± 0.17） h, respectively. Relative bioavailability of EABLN to EAB was 143%, the bioequivalence of AUC（0—72 h） and Cmax in EAB and EABLN were eligible, but bioequivalence of tmax was not eligible. Conclusion EABLN improved the pharmacokinetics of EAB in rats, meanwhile, oral bioavailability of EAB was significantly increased, and there was not bioequivalence between EABLN and EAB.

关 键 词：吴茱萸碱 吴茱萸碱丁酰基衍生物 固体脂质纳米粒 药动学 生物等效性 

分 类 号：R285.5[医药卫生—中药学]