摘要
目的 比较自制羟基喜树碱脂质体注射液 (hydroxycamptothecinliposomesinjection ,L HCPT)和市售羟基喜树碱注射液 (markethydroxycamptothecininjection ,M HCPT)在家兔体内的药代动力学行为。方法 分别静脉注射单剂量 ( 1mg kg)的L HCPT和M HCPT ,用HPLC法测定血浆中的药物浓度 ,用 3p87程序和SPSS软件处理和分析数据 ,计算有关药代动力学参数。结果 经 3p87程序拟合 ,家兔静脉注射单剂量L HCPT和M HCPT后 ,其血药浓度 时间数据分别符合权重为1 C C的二室模型 ;静脉注射L HCPT和M HCPT后Cmax分别为 3 1768、1 5 2 19μg ml,t1 2 β分别为 3 3 990 7、2 9 3 92 9min ,AUC分别为 2 8 85 15、11 65 5 1μg·min·ml- 1 ,CL分别为 0 .0 3 5 0、0 0 860L·min- 1 ·kg- 1 ,Vc分别为 0 2 70 0、0 64 0 0L kg ,可见L HCPT比M HCPT注射后具有更高的血药浓度水平 ,较长的消除半衰期 ,更大的血药浓度 时间曲线下面积 ,较低的总体清除率和较小的表观分布容积。结论 L HCPT和M HCPT在家兔体内的一些重要的药代动力学特性发生了明显改变 。
Objective To compare the pharmacokinetic characteristics of hydroxycamtothecin liposomes injection (L HCPT) with market hydroxycamtothecin injection (M HCPT) in rabbits administrated intravenously. Methods L HCPT and M HCPT were intravenously administrated to rabbits at a single dosage of 1 mg/kg. The HCPT plasma concentrations were determined by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated and analyzed using 3P87 program and SPSS software. Results The concentration time data of L HCPT and M HCPT after a single intravenous administration were fitted to two compartment model with a weight of 1/C/C. The Cmax of L HCPT and M HCPT was 3 176 8 μg/ml and 1 521 9 μg/ml. t 1/2β was 33 990 7 min and 29.392 9 min. AUC was 28.851 5 μg·min·ml -1 and 11.655 1 μg·min·ml -1 . CL was 0 035 0 L·min·kg -1 and 0.086 0 L·min·kg -1 . Vc was 0.270 0 L/kg and 0 640 0 L/kg, respectively. Compared with those of M HCPT, higher plasma concentration levels, longer elimination of half life, larger area under the curve values and lower clearance, smaller apparent volume of distribution of L HCPT were found. Conclusion There are obvious changes of pharmacokinetic properties of L HCPT and M HCPT after injection to rabbits, which is helpful to improve the therapeutic effect of HCPT.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2004年第6期517-519,共3页
Journal of Third Military Medical University
关键词
羟基喜树碱
药代动力学
脂质体
高效液相色谱法
hydroxycamptothecin
pharmacokinetics
liposome
high performance liquid chromatography
