紫杉醇纳米乳剂的体内外考察  

Studies on hypersensitivity and pharmacokinetics of paclitaxel microemulsion

作　　者：何蕾[1] 王桂玲[1] 张强[1] 

机构地区：[1]北京大学药学院药剂研究室,北京100083

出　　处：《药学学报》2003年第3期227-230,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 (3 9870 897)

摘　　要：目的　考察紫杉醇纳米乳剂的形态、粒径分布及急性过敏反应 ,研究紫杉醇注射剂及自制紫杉醇纳米乳剂在大鼠体内的药代动力学。方法　用HPLC法测定大鼠体内紫杉醇含量。数据用 3P87处理 ,得到各主要药代动力学参数。结果　纳米乳剂平均粒径为 17 2nm。纳米乳剂急性过敏反应为阴性 ,而市售紫杉醇注射液急性过敏反应为阳性。血浆中杂质及制剂中辅料不干扰紫杉醇的测定。大鼠iv自制紫杉醇纳米乳剂及紫杉醇注射液后的药 时曲线均符合二室模型。数据用 3P87处理 ,得到各主要药代动力学参数。纳米乳剂及注射液的K1 0 分别为 0 5 7,1 2 9·h- 1 ,K1 2 分别为 1 4 4 ,1 2 7·h- 1 ,K2 1 分别为 3 0 8,0 5 1·h- 1 ,AUC分别为 34 98,2 1 85mg·h·L- 1 。结论　紫杉醇纳米乳剂较紫杉醇注射液毒性降低 。Aim To evaluate the hypersensitivity reaction of the blank paclitaxel microemulsion and study the O/W paclitaxel microemulsion′s pharmacokinetics in rats. Methods An alternative paclitaxel microemulsion was prepared with small particle size. The hypersensitivity reaction of the blank microemulsion was investigated in guinea pigs. In pharmacokinetic study, 5 rats were given iv Taxol or paclitaxel microemulsion. Blood samples were collected at 0, 0 25, 0 5, 1, 2, 4, 6, 8, 10, 12, 14 h and the concentration of paclitaxel in plasma was determined by HPLC method. The data obtained were processed using 3P87 program. Results The mean size of the microemulsion is 17 2 nm. The preparation of blank microemulsion did not show any hypersensitivity, while the injection of commercial product showed significant hypersensitivity. The concentration time curve of paclitaxel microemulsion and commercial injection (Taxol) fitted a two compartment model. The K 10 , K 12 , K 21 and AUC of paclitaxel microemulsion were 0 571·h -1 , 1 441·h -1 , 3 081·h -1 and 34 98 mg·h·L -1 . Those of commercial injection were 1 291·h -1 , 1 271·h -1 , 0 511·h -1 and 21 85 mg·h·L -1 . Conclusion The blank paclitaxel preparation of micoemulsion reduced the hypersensitivity in guinea pigs compared with the blank commercial injection. The paclitaxel microemulsion has relatively longer circulating time in rats.

关 键 词：紫杉醇 纳米乳剂 急性过敏反应 HPLC 药代动力学 

分 类 号：R943.41[医药卫生—药剂学] R945.2[医药卫生—药学]