盐酸阿霉素及其脂质体在大鼠体内的相关药动学参数比较

The pharmacokinetic comparsion of Hydrochloric Doxorubicin injections and Hydrochloric Dox-orubicin liposomes in rats

目的 比较盐酸阿霉素脂质体与盐酸阿霉素在大鼠体内的血药浓度及相关药动学参数。方法 采用HPLC法,测定大 鼠经尾静脉注射盐酸阿霉素或盐酸阿霉素脂质体注射液[0.8 mg·(100 g)-1体重]后,在大鼠体内的血药浓度,得出药-时曲线图及相关药动学参数,并将血药浓度经SPSS10.0统计软件进行配对t检验。结果 在大鼠体内,阿霉素脂质体血药浓度200倍于阿霉素血药浓度;阿霉素脂质体药时曲线下面积AUC较阿霉素大,表观分布容积Vc较阿霉素小,清除率Cl(s)较阿霉素慢;阿霉素与阿霉素脂质体在大鼠体内的血药浓度具有显著性差异(P<0.05)。结论 阿霉素制成脂质体可延长其在血浆中的停留时间,降低血管外分布量,减慢清除。可望提高药效、降低心脏的不良反应。

OBJECTIVE To compare the differences of pharmacokinetics parameters of Hydrochloric Doxorubicin injections and liposomes. METHODS An HPLC assay method was established to estimate the blood concentrations of Hydrochloric Doxorubicin after caudal vein administration of 0.8 mg·(100 g)-1 weigh.The blood concentration- time curves as well as correlated pharmaciokinetics parameters were obtained. Moreover, the data were checked with T-test. RESULTS In rats, the blood concentration of Doxorubicin liposomes was 200 times of that of Doxorubicin injections. Compared with Doxorubicin injections, Doxorubicin liposomes had bigger AUC, Smaller Vc and slower Cl(s). The blood concentrations between Doxorubicin liposomes and Doxorubicin injections in rats presented significant difference( P < 0.05). CONCLUSION The maintenance time in plasm of Doxorubicin is extended in the liposomes formulation. It can also decrease distribution in estra -blood vessel and decrease the speed of clearance, and can raise therapy effect and decrease heart toxicity.