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目的:考察紫杉醇纳米混悬剂在大鼠体内的药动学及小鼠体内的组织分布情况。方法:将紫杉醇注射液和紫杉醇纳米混悬剂2种制剂静脉给药后,采用HPLC法分别测定给药后5,10,15,30min及1,2,4,6,8,12h时大鼠的血药浓度,给药后5,15,30min及1,2,4,8,12h时紫杉醇在小鼠心、肝、脾、肺、肾、脑组织中的含量,对2种制剂的体内生物分布特征和靶向性进行评价。结果:大鼠血浆中,紫杉醇纳米混悬剂和紫杉醇注射液的消除相半衰期分别为(5.6±0.7)和(3.8±0.4)h;AUC分别为(5.2±0.4)和(20.3±1.1)mg.h.L-1;MRT分别为(3.2±0.4)和(2.8±0.3)h;Cl分别为(2.05±0.22)和(0.56±0.19)L.kg-1.h-1。与紫杉醇注射液相比,紫杉醇纳米混悬剂在肝、脾、脑组织中的药物含量显著增加。结论:相对于市售紫杉醇注射液,紫杉醇纳米混悬剂向靶部位富集,显著降低了非靶器官的药物浓度,可减轻制剂不良反应,使药物在血浆中的循环时间延长。
Objective: To investigate the pharmacokinetics of paclitaxel nanosuspensions in rats and the tissue distribution in mice. Methods: Paclitaxel injection and paclitaxel nanosuspension two kinds of preparations after intravenous administration, respectively, by HPLC assay after administration 5,10,15,30 min and 1,2,4,6,8,12 h rat , The content of paclitaxel in mouse heart, liver, spleen, lung, kidney and brain at 5, 15, 30min and 1, 2, 4, 8 and 12h after administration, Biodistribution characteristics and targeting were evaluated. Results: The elimination half-lives of paclitaxel nanosuspension and paclitaxel injection were (5.6 ± 0.7) and (3.8 ± 0.4) h respectively in rat plasma. The AUC were (5.2 ± 0.4) and (20.3 ± 1.1) mg (2.0 ± 0.22) and (± 0.56 ± 0.19) L · kg-1.h-1, respectively. Compared with paclitaxel injection, paclitaxel nanosuspension significantly increased the drug content in liver, spleen and brain. CONCLUSION: Paclitaxel nanosuspensions enrich the target site relative to the commercially available paclitaxel injection, significantly reducing the drug concentration in non-target organs, alleviating adverse drug reactions and prolonging the circulation time of the drug in plasma.