摘要
目的 比较碾碎的泊沙康唑肠溶片和混悬液家兔灌胃给药后的药代动力学.方法 6只新西兰兔用随机自身交叉对照试验设计,分别灌胃给予碾碎的泊沙康唑肠溶片或泊沙康唑混悬液,给药后于特定的时间点取血,分离血浆并处理后用高效液相色谱法测定血浆中泊沙康唑的浓度,用DAS 2.0软件拟合药代动力学参数.结果 泊沙康唑肠溶片和混悬液组的AUC0-t分别为(40.03±5.04)和(49.92±16.09)μg·mL-1·h,AUC0-∞ 分别为(44.00±4.50)和(51.10±16.80)μg·mL-1·h,t1/2分别为(7.30±1.13)和(8.53±1.34)h,Cmax分别为(3.12±0.57)和(2.78±0.60)μg·mL-1,表观分布容积(Vd)分别为(2.40±0.34)和(2.59±0.76)L·kg-1,清除率(CL)分别为(0.23±0.02)和(0.22±0.08)L·h-1·kg.2 组的 AUC0-t、Cmax和Vd比较,在统计学上差异均无统计学意义(均P＞0.05).结论 碾碎的泊沙康唑肠溶片对比混悬液无药代动力学优势.
Abstract
Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)µg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.
基金项目
山东省自然科学基金资助项目(ZR2021QH145)
山东省药学会医院合理用药天际健康中青年科研学术活动基金资助项目(hlyy2021-04)
国家科技期刊平台
NSTL
万方数据