多西他赛自微乳注射液在大鼠体内药动学及组织分布

Pharmacokinetics and Tissue Distribution of Docetaxel Self-microemulsifying Drug Delivery System for Injection in Rats

目的测定大鼠单剂量(12.55 mg/kg)尾静脉注射多西他赛自微乳溶液和市售注射剂的血药浓度,比较2组的药动学行为;研究多西他赛自微乳溶液和市售注射剂在正常大鼠心,肝,脾,肺,肾中的分布情况。方法采用高效液相法测定SD大鼠给药后不同时间点的血药浓度以及组织分布情况。结果多西他赛自微乳溶液组和市售制剂组的主要药动学参数除表观分布容积V1/F外,t1/2β、CL、AUC0→∞、MRT0→∞均无显著性差异(P>0.05)。结论自制微乳与市售制剂在大鼠体内具有相似的动力学特征,没有显著改善药物在大鼠体内的组织分布。

Objective To determine the plasma concentrations of docetaxel （12.5 mg/kg） self-microemulsifying drug delivery system and injection form the market after injected in caudal vein of rats, and to compare the pharmacokinetic behavior of the 2 groups. To determine the distribution of docetaxel in heart, liver, spleen, lung, and kidney of rats. Methods The concentration of docetaxel in plasma and tissues were tested by HPLC after a single does injection at various time points. Results There was no significant difference （P 〉0.05） of main pharmacokinetic parameters t1/2β, CL, AUC0→∞ , MRT0→∞, between 2 groups, except apparent volume of distribution （V1/F）. Conclusion The self-microemulsifying and the commercial preparations of docetaxel have similar kinetic characteristics, and has no significant improvement for the tissue distribution in rats.