多西他赛脂肪乳注射液在大鼠体内的药代动力学研究

Pharmacokinetic behavior of docetaxel lipid emulsion injection in rats

制备多西他赛脂肪乳注射液,并考察大鼠尾静脉给药后体内的药代动力学行为。采用高压均质法制备多西他赛脂肪乳注射液,将12只Wistar大鼠随机分为多西他赛脂肪乳注射液组和多西他赛注射液组,尾静脉给药剂量均为6 mg/kg,采用HPLC法测定大鼠血中多西他赛的浓度,采用3P97程序计算多西他赛药代动力学参数。多西他赛脂肪乳注射液平均粒径为(221.6±13.4)nm,聚合物分散指数(PDI)为0.092±0.003,Zeta电位为-30.3 m V。多西他赛脂肪乳注射液和多西他赛注射液在大鼠体内的t_(1/2(α))分别为(0.072±0.014)和(0.066±0.015)h;t_(1/2(β))分别为(0.573±0.253)和(0.432±0.184)h;AUC_(0-12 h)分别为(7.98±1.25)和(6.26±1.83)μg·h/m L。多西他赛脂肪乳注射液与市售多西他赛注射液相比,在大鼠体内具有相似的药代动力学特征,药代动力学过程均符合双室模型。

The aim of this study was to prepare and characterise docetaxel lipid emulsion injection and to con- duct the characterization of its pharmacokinetics in rats after tail-vein injection. High pressure homogenization method was used to prepare docetaxel lipid emulsion. 12 Wistar rats were randomly divided into docetaxel lipid emulsion injection group and docetaxel injection group, and dosed at 6 mg/kg through tail-vein injection. Docetaxel concentration in plasma was determined by HPLC. The pharmacokinetic parameters of docetaxel in rats were obtained using the 3P97 program. Particle size, polydispersion index, Zeta potential of docetaxel lipid emul- sion were found to be （221.6 ± 13.4） nrn, （0. 092 ± 0. 003） and - 30. 3 mV, respectively, t1/2（α） of docetaxel lipid emulsion injection and docetaxel injection were （0.072 ± 0.014）and （0.066±0.015）h; t1/2（β） were （0. 573 ±0. 253） and （0. 432 ±0. 184） h; AUC0-12h were （7.98 ± 1.25） and （6.26 ± 1.83） μg·h/mL, respec- tively. Docetaxel lipid emulsion injection had similar pharmacokinetie characteristics to docetaxel injection. The pharmacokinetic data obtained for both preparations fitted a two-compartment model.