盐酸雷洛昔芬自微乳在大鼠体内的药动学评价  

Pharmacokinetic evaluation after oral administration of raloxifene hydrochloride self-microemulsion in rats

作　　者：卢秀霞[1] 何琳[1] 李敏媛[2] 陈锦娜 

机构地区：[1]广东药学院医药化工学院,中山528458 [2]广东药学院中药学院,中山528458

出　　处：《中国新药杂志》2015年第8期936-941,共6页Chinese Journal of New Drugs

基　　金：广东省医学科研基金(B2014210);广东省科技计划项目(粤科规划字[2013]137号)

摘　　要：目的：考察盐酸雷洛昔芬自微乳在大鼠体内的药动学行为及生物利用度。方法：分别按100mg·kg-1灌胃给予盐酸雷洛昔芬自微乳与市售片剂,采用HPLC法测定大鼠血浆盐酸雷洛昔芬浓度,DASTM ver 2.0药动学软件计算并比较药动学参数。结果：血浆盐酸雷洛昔芬浓度在0.05~3.00μg·m L-1呈良好线性关系,r=0.999 8,萃取回收率为94.38%~98.29%;盐酸雷洛昔芬自微乳与市售片剂的药动学过程均符合一室模型,权重因子为1;盐酸雷洛昔芬自微乳的达峰浓度（Cmax）、平均滞留时间（MRT）、药时曲线下面积（AUC0~t）分别是市售片剂的1.58倍（P〈0.001）、1.26倍（P〈0.05）、2.11倍（P〈0.001）,相对生物利用度为211.43%。结论：HPLC法准确、灵敏。自微乳能增加盐酸雷洛昔芬的溶解度,有利于提高口服生物利用度,从而改善胃肠道吸收。Objective： To investigate the in vivo pharmacokinetic behavior and the bioavailability after oral administration of raloxifene hydroehloride self-microemulsion in rats. Methods： Raloxifene hydrochloride self-mi- croemulsion and the commercially available tablets at a single dose of 100 mg· kg^-1 were given, respectively, through intragastric administration. An HPLC method was established to determine the concentration of raloxifene hydrochloride in rat plasma. The pharmacokinetie parameters were calculated and compared using DASTM ver 2.0 pharmacokinetic software. Results： The linear correlation was satisfactory when the concentration of raloxifene hydrochloride in rat plasma was 0.05 - 3.00 μg· mL^-1 , r = 0. 999 8. The extraction recovery was 94.38% - 98.29%. The pharmacokinetic process were conformed to fit the one-compartment model for both raloxifene hydrochloride self-microemulsion and commercially available tablets with the weighting factor of 1. The peak concentra tion （ Cmax） , mean residence time （MRT） , and the area under the concentration-time curve （ AUC0-t ） of ralox- irene hydrochloride self-microemulsion were 1.58 （P 〈 0. 001 ）, 1.26 （ P 〈 0.05 ） and 2.11 （P 〈 0. 001 ） times of commercially available tablets, respectively, and the relative bioavailability was 211. 43%. Conclusion： The HPLC method is accurate and sensitive. Self-microemulsion is able to increase the solubility of raloxifene hydrochloride, improve the oral bioavailability and gastrointestinal absorption.

关 键 词：盐酸雷洛昔芬 自微乳 高效液相色谱 药动学评价 口服生物利用度 

分 类 号：R969.1[医药卫生—药理学]