He Lei, Wang Gui-ling, Zhang Qiang
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, People's Republic of China.
Int J Pharm. 2003 Jan 2;250(1):45-50. doi: 10.1016/s0378-5173(02)00478-7.
Based on the clinical fact that paclitaxel injection (Taxol) frequently causes hypersensitivity reactions, we prepared an alternative paclitaxel microemulsion with small particle size (17.2 nm). The hypersensitivity evaluation and pharmacokinetic behavior in rats were conducted to assess the new microemulsion. The results showed that the new microemulsion was negative and the placebo Taxol solution was positive with regard to allergic reactions. In the pharmacokinetic study, five rats were administrated Taxol or paclitaxel microemulsion. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 14 h and paclitaxel determined by HPLC. The area under the curve (AUC) was significantly higher in the microemulsion group (34.98 microg ml(-1) h) than that in the Taxol group (21.98 microg ml(-1) h). Also, the K(10) was much smaller in the microemulsion group (0.57 h(-1)) compared with the Taxol group (1.29 h(-1)), showing the elimination rate was much slower in the former than in the latter. Compared with Taxol, the paclitaxel microemulsion caused less toxicity and had a longer circulation time in rats.
基于紫杉醇注射液（泰素）常引起过敏反应这一临床事实，我们制备了一种粒径较小（17.2纳米）的替代紫杉醇微乳剂。对大鼠进行了过敏反应评估和药代动力学行为研究，以评价这种新型微乳剂。结果显示，新型微乳剂在过敏反应方面呈阴性，而安慰剂紫杉醇溶液呈阳性。在药代动力学研究中，给5只大鼠分别注射紫杉醇或紫杉醇微乳剂。在0、0.25、0.5、1、2、4、6、8、10、12、14小时采集血样，并用高效液相色谱法测定紫杉醇含量。微乳剂组的曲线下面积（AUC）（34.98微克·毫升-1·小时）显著高于紫杉醇组（21.98微克·毫升-1·小时）。此外，微乳剂组的K(10)（0.57小时-1）比紫杉醇组（1.29小时-1）小得多，表明前者的消除速率比后者慢得多。与紫杉醇相比，紫杉醇微乳剂在大鼠体内的毒性较小，循环时间更长。
