Zhang Xue-Nong, Tang Li-Hua, Gong Jin-Hong, Yan Xue-Ying, Zhang Qiang
College of Pharmacy, Soochow University, Suzhou 215123, People's Republic of China.
PDA J Pharm Sci Technol. 2006 Mar-Apr;60(2):89-94.
Based on the clinical fact that paclitaxel injection (Taxol) frequently causes hypersensitivity reactions, an alternative paclitaxel self-emulsifying microemulsion was studied with phase diagrams, and the prescription of microemulsion formulation was optimized. Regarding Taxol, the pharmacokinetic parameters of microemulsion and hypersensitivity were investigated in rats and guinea pigs, respectively. The results showed that the self-emulsifying microemulsion was made up of tricaproin:tributyrin 1:1 as the oil phase, ethanol as assist, pluronic F68 and lecithin as emulsifier, and formed a mean diameter of 16 +/- 3 nm when diluted with saline. In the pharmacokinetic study, rats were administrated Taxol or paclitaxel microemulsion. Blood samples were collected at definite time intervals, and plasma concentrations of paclitaxel were determined by high-performance liquid chromatography. The area under the curve was significantly higher in the microemulsion group (33 mg.ml(-1).h) than that in the Taxol group (25 mg.ml(-1).h) (P < 0.01). The constant of transport rate of speed, K10 (0.55 h(-1)), was much smaller in the microemulsion group compared with the Taxol group (1.55 h(-l)). The mean retention time was 3.89 h in microemulsion group and 2.52 h in the Taxol group, 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）频繁引起过敏反应这一临床事实，利用相图研究了一种替代的紫杉醇自乳化微乳，并优化了微乳制剂的处方。对于泰素，分别在大鼠和豚鼠中研究了微乳的药代动力学参数及过敏反应。结果表明，该自乳化微乳由辛酸甘油酯：丁酸甘油酯1:1作为油相、乙醇作为助乳化剂、泊洛沙姆F68和卵磷脂作为乳化剂组成，用生理盐水稀释后平均粒径为16±3nm。在药代动力学研究中，给大鼠分别注射泰素或紫杉醇微乳。在确定的时间间隔采集血样，用高效液相色谱法测定血浆中紫杉醇的浓度。微乳组的曲线下面积（33mg·ml⁻¹·h）显著高于泰素组（25mg·ml⁻¹·h）（P<0.01）。微乳组的转运速率常数K10（0.55h⁻¹）远小于泰素组（1.55h⁻¹）。微乳组的平均滞留时间为3.89h，泰素组为2.52h，表明前者的消除速率比后者慢得多。与泰素相比，紫杉醇微乳在大鼠中引起的毒性较小且循环时间更长。
