关键词: 9-硝基喜树碱, 药代动力学, 犬, 高效液相色谱, 液相-质谱联用

Abstract: 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.

Key words: 9-nitro-camptothecin, pharmacokinet-ics, dogs, HPLC, HPLC-MS