摘要
采用荧光法测定血和织组中MTX含量,用阻尼非线性最小二乘法及矩量法处理和比较MTX多相脂质体(PL—MTX)及MTX水溶液(F-MTX),尾静脉一次给药18mg/kg后,9hr内小鼠体内的药物动力学和药物分布。得到PL-MTX的药-时曲线为:C(μg)=30.5e^(-3.771)+3.27e^(0.381),具有开放二房室模型特征,清除率Cl:为927ml/h,血药平均滞留时间MRT为100min;F-MTX的药-时曲线为:C(μg)=39.7e^(-13.2t)+15.1e^(-2.77t)+0.633e^(-0.216t),具有开放三房室模型特征,Cl_s为1579ml/h,MRT为57min。两者结果存在显著差异。另外,PLMTX较F-MTX在脾、肺、肝、骨髓的药量分布有显著提高。表明多相脂质体剂型可能增加化疗药物在上述器官为病灶的癌细胞的药物浓度。
In this paper, a comparison of Pharmacokinetics and drug distribution afterintravenous injection of both PL-MTX and F-MTX into L615 mice is reported.The results show PL-MTX and F-MTX plasma drug concentration-time curvesreflected two and three compartmental characterristics, respectively. PL-MTX canmaintain plasma drug concentration at higher level and for a longer time thanF-MTX. The amount of MTX in spleen, lung, bone marrow was found signifi-cantly higher after injection of PL-MTX than F-MTX.This implies that PL-MTXprobably has some advantages over F-MTX in the treatment of leukemias.
关键词
甲氨喋呤
药代动力学
体内分布
Methotrexate
Polyphase liposome
Pharmacokinetics
Compartment model
Body distribution
