[Studies on hypersensitivity and pharmacokinetics of paclitaxel microemulsion].
OBJECTIVE
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 i.v. 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 K10, K12, K21 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.


CONCLUSIONS
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.
He
Lei
L
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Wang
Gui-ling
GL
Zhang
Qiang
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004342:Drug Hypersensitivity / Q000209:etiology*; D004655:Emulsions; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D051381:Rats
D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D017239:Paclitaxel