VM-26小鼠腹腔内应用药物动力学研究

目的 :测定VM - 2 6(鬼臼噻吩甙 )腹腔内应用后的血浆药代动力学参数 ,肝脏、肾脏、肠壁的药物浓度分布 ,为治疗卵巢癌腹腔化疗提供理论依据。方法 :1 50只小鼠随机分为两组 (30mg/kg和 50mg/kg)腹腔给药 ,血药浓度及肝、肾、肠壁内药物浓度 ,测定用高效液相法 (HPLC) ,数据用 3P87软件处理。结果 :30mg/kg、50mg/kg血浆药物浓度 (Cmax)分别为 9.53mg/L和 1 9.1 8mg/L ,峰浓度时间 (Tpeak)分别为 2 .2 7h和 3 .2 1h ,药———时曲线下面积(AUC)分别为 79.32mg/ (h·L)和 2 0 7.95mg/ (h·L) ,三者经统计学处理有显著性差异 (P <0 .0 0 1 ) ,证明腹腔内给药剂量不同 ,上述三项参数呈剂量依赖性关系。两剂量组的表观分布容积 (V)分别为 2 .61L和 1 .48L ,经统计学处理P <0 .0 5 ,即给药剂量不同 ,表观分布容积也不相同。血浆清除半衰期 (t1 / 2 )两剂量组分别为 8.66h和 6 .76h ,血浆清除率分别为 0 .73mg/ (kg·h)与 0 .31mg/ (kg·h) ,前者经统计学处理P >0 .1 0。表明剂量不同 ,其半衰期无差异。组织中药物浓度分布从高到低的是 :肠壁、肝脏、肾脏 ,但达高浓度值的时间不恒定 ,一般在 0 .5～ 2h之间 ,8h下降至最低点 ,1 2h又略有上升。讨论 :VM - 2 6腹腔内注射 ,对于治疗卵巢癌是安全、可靠、毒性小的

The pharmacokinetics study about intraperitoneal administration of VM-26 in mice

Objective To research feasibility of intraperitoneal administration of VM-26,the pharmacokinetics in the plasma of mice,the concentration and distribution of VM-26 in liver?kidneys and intestinal wall were determined.Method The mice used for study were equally divided into 2 groups according to the intraperitoneal dosage(30 mg/kg and 50 mg/kg).The concentration and distribution of VM-26 in the plasma and the tissues were determined by high-performance liquid chromatography(HPLC).The pharmacokinetics parameters were processed with 3p87 software.Results The results showed an obvious difference between 30 mg/kg and 50 mg/kg groups.Cmax in the plasma was 9.53 mg/L and 19.18 mg/L( P <0.001),AUC was 79.32 mg/h/L and 207.95 mg/h/L,Tpeak was 2.27 h and 3.21 h ( P <0.001) and V/F was 2.61 L and 1.48 L( P <0.05) respectively,but t 1/2β exhibited no difference (8.66 h and 6.76 h P >0.10) and CL was 0.37 mg/kg/h and 0.31 mg/kg/h respectively,The level of VM-26 in the tissue arranged from high to low were intestinal wall?liver and kidneys.Conclusion The studies indicates that the intraperitoneal chemotherapy of VM-26 in curing ovarian cancer is a feasible,securable and valuable method.