9-硝基喜树碱犬体内药代动力学研究

目的: 研究9-硝基喜树碱在犬体内药动学规律。方法: 犬静注或灌服3个剂量9-硝基喜树碱,血浆9-硝基喜树碱浓度用高效液相色谱法及液相-质谱联用法检测,浓度-时间数据用3P97药代动力学软件进行分析,计算药动学参数,分析AUC、C_max及ke与剂量的线性关系。结果: 犬静注0.5、1、2mg·kg^-19-硝基喜树碱,t_1/2分别为2.2±2.2、1.8±1.7和0.8±0.6h;AUC_0-t分别为105±71、272±81和396±93ng·h·ml^-1;犬灌胃1、2、4mg·kg^-19-硝基喜树碱,C_max分别为9.3±8.2、42.2±35.7和63.6±5.9ng·ml^-1,T_max分别为0.3±0.1、0.2±0.1、0.4±0.1h,t_1/2分别为1.9±1.3、1.0±0.6和2.8±1.5h,AUC_0-t分别为8.9±7.2、16.3±12.3和59.5±25.5ng·h·ml^-1;各剂量组t_1/2及k_e与剂量无关(P>0.05);口服生物利用度<6%。结论: 静脉及灌胃给药后,9-硝基喜树碱在犬体内的动力学过程符合二室模型,在本实验所用的剂量范围内为线性动力学过程。9-硝基喜树碱灌胃给药后吸收迅速,口服生物利用度低。

Pharmacokinetics of 9-nitro-camptothecin in Beagle dogs

AIM: To study the pharmacokinetics of 9-nitro-camptothecin(9-NC)in dogs.METHODS: Each Beagle dog was given a single dose of 9-NC by iv orig administration.The concentrations of 9-NC in plasma were detected by HPLC and HPLC-MS.Pharmacokinetic parameters were determined from the plasma concentra-tion-time data with the 3P97 software package.The rela-tionships betweenAUC,C max orke and dose were evaluat-ed by linearregression.RESULTS: Afteriv administra-tion of 9-NC at the dose of 0.5,1,and 2 mg·kg^-1,the t_1/2values of 9-NC were 2.2±2.2,1.8±1.7 and 0.8±0.6 h,respectively,and AUC_0-twere 105±71,272±81 and 396±93 ng·h·ml^-1,respectively.Afterig ad-ministration of 9-NC at the dose of 1,2,and 4 mg·kg^-1,9-NC was rapidly absorbed,reaching C_maxof 9.3±8.2,42±36 and 64±6 ng·ml^-1at T_maxof 0.3±0.1,0.2±0.1,0.4±0.1 h,respectively,the t_1/2values of 9-NC were 1.9±1.3,1.0±0.6 and 2.8±1.5 h,respective-ly,and AUC_0-twere 8.9±7.2,16±12 and 60±26ng·h·ml^-1,respectively.The values of t_1/2and ke of 9-NC were independent of dose(P>0.05).The absolute oral bioavailability of 9-NC was less than 6%.CONCLUSION: Afteriv orig administration of 9-NC,the time course of plasma concentration in dogs complieswith a two-compartment model.The kinetic process of 9-NC in dogs is linearin the range of the experimental dosage.9-NC is absorbed rapidly afterig administration and the oral bioavailability is poor.