[Preparation of docetaxel liposomes and their pharmacokinetics in rabbits].

BACKGROUND & OBJECTIVE: Docetaxel is used to treat non-small cell lung cancer, breast cancer and ovarian cancer. It is indissolvable and the solvent containing polysorbate-80 and 13% solution of ethanol is used for injections. Its clinical application is limited because of frequent severe hypersensitive responses. This study was to prepare docetaxel (DOC) liposomes and investigate their pharmacokinetics in rabbits after intravenous administration. METHODS: DOC liposomes, with or without modification of polyethylene glycol (PEG), were prepared by thin-film ultrasonic dispersion method. The entrapment efficiency and mean diameter of the liposomes were measured. After intravenous administration in rabbits, plasma DOC concentration was detected by solid phase extraction high-performance liquid chromatography (SPE-HPLC). The pharmacokinetic parameters were calculated and analyzed by 3p87 pharmacokinetic program. RESULTS: The entrapment efficiency of DOC liposomes was above 75%. The mean diameter was about 150 nm. The half-life of distribution (T(1/2alpha)) were (0.17+/-0.04) h for market docetaxel injection (M-DOC), (0.31+/-0.11) h for common DOC liposome (L-DOC), and (0.32+/-0.06) h for PEG-2000-modified DOC long circulating liposome (PEG-DOC-LCL); the half-life of clearance (T(1/2beta)) were (8.54+/-1.05), (11.18+/-1.33), and (10.51+/-1.13) h, respectively; the apparent volume of distribution (V(d)) were (13.66+/-3.62), (8.65+/-1.11), and (6.31+/-0.55) L, respectively; the area under the concentration-time curve from 0 to 24 h (AUC(0-->24)) were (13.45+/-2.44), (22.83+/-3.57), and (29.31+/-5.96) mg x (h x L)(-1), respectively; the area under the concentration-time curve from 0 to infinity h (AUC(0-->infinity)) were (15.07+/-2.76), (28.70+/-4.95), and (36.95+/-9.13) mg x (h x L)(-1), respectively; the clearance (CL) were (1.10+/-0.18), (0.54+/-0.08), and (0.42+/-0.07) L/h, respectively. CONCLUSION: The thin-film prepared DOC liposomes have high entrapment efficiency and small particle size. Both liposomes, especially PEG-DOC-LCL, can raise AUC and prolong the resident time of drugs in the blood circulating system.