An alternative paclitaxel microemulsion formulation: hypersensitivity evaluation and pharmacokinetic profile.
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.
He
Lei
L
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, People's Republic of China.
Wang
Gui-ling
GL
Zhang
Qiang
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004342:Drug Hypersensitivity / Q000209:etiology*; D004655:Emulsions; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity
D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol