多烯紫杉醇磷脂纳米粒在大鼠体内药代动力学及生物利用度研究

Pharmacokinetics and bioavailability of docetaxel-loaded lecithin nanoparticles in rats

目的研究多烯紫杉醇口服磷脂纳米粒在大鼠体内的药代动力学和口服生物利用度。方法大鼠尾静脉注射多烯紫杉醇注射剂(20μg/g),大鼠单剂量灌胃给予20μg/g多烯紫杉醇溶液,含环孢素A的多烯紫杉醇溶液或含相等剂量多烯紫杉醇的磷脂纳米粒。采用高效液相色谱法检测给药后各时间点血浆中的多烯紫杉醇浓度,评价药代动力学参数和生物利用度。结果多烯紫杉醇口服磷脂纳米粒单剂量灌胃给药后Cmax为(116.19±28.58)pg/L,tmax为1 h,MRT为(5.60±0.34)h,AUC为(490.74±37.28)h.pg.L-1,口服生物利用度是溶液剂的3.65倍。结论磷脂纳米粒能够显著提高多烯紫杉醇的口服生物利用度。

Objective To study the pharmacokinetics and bioavailability of docetaxel-loaded lecithin nanoparticles in rals. Methods Marketed docetaxel injections were intravenously administered to rats at a dose of 20 μg/g. Doeetaxel solution or docetaxel-loaded lecithin nanoparticles was administered orally at a single dose of 20 μg/g. HPLC method was applied to determine the plasma concentralion of docetaxel. Pharmacokinetics and bioavailability of docetaxel-loaded lecithin nanoparticles were investigated in rats after oral administration. Results After single oral administration of docetaxel-loaded lecithin nanoparticles, the calculated Cmaxwas （116.19±28.58） pg/L, tmaxwas 1 h,MRTwas （5.60±0.34） h and AUC was （490.74 ＋37.28） h ·pg· L^-1 The oral bioavailability of docetaxel-loaded lecithin nanoparticles was 3.65 times of that of docetaxel solution. Conclusion The lecithin nanoparticles can significantly improve the oral bioavailability of docetaxel.