泊沙康唑肠溶片碾碎给药对比口服混悬液家兔体内药代动力学研究  

Pharmacokinetic study of crushed posaconazole enteric-coated tablets compared with oral suspension in rabbits

作　　者：刘凤喜 李斯雯 宗慧颖 张武林 黄欣[1] 李妍[1] LIU Feng-xi;LI Si-wen;ZONG Hui-ying;ZHAG Wu-Lin;HUANG Xin;LI Yan(Department of Clinical Pharmacy,The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,Shandong Engineering and Technology Research Center for Pediatric Drug Development,Shandong Medicine and Health Key Laboratory of Clinical Pharmacy,Jinan 250014,Shandong Province,China;College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong Province,China;Qilu Animal Health Products Co.,Ltd,Jinan 250100,Shandong Province,China)

机构地区：[1]山东第一医科大学第一附属医院(山东省千佛山医院)临床药学,山东省儿童药物临床评价与研发工程技术究中心,山东省医药卫生临床药学重点实验室,山东济南250014 [2]山东中医药大学药学院,山东济南250355 [3]齐鲁动物保健品有限公司,山东济南250100

出　　处：《中国临床药理学杂志》2024年第17期2543-2547,共5页The Chinese Journal of Clinical Pharmacology

基　　金：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)。

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AUC_(0-t)分别为(40.03±5.04)和(49.92±16.09)μg·mL^(-1)·h,AUC_(0-∞)分别为(44.00±4.50)和(51.10±16.80)μg·mL^(-1)·h,t_(1/2)分别为(7.30±1.13)和(8.53±1.34)h,C_(max)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AUC_(0-t)、C_(max)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。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:AUC_(0-t)were(40.03±5.04)and(49.92±16.09)μg·mL^(-1)·h;AUC_(0-∞)were(44.00±4.50)and(51.10±16.80)μg·mL^(-1)·h;t_(1/2)were(7.30±1.13)and(8.53±1.34)h;Cmax 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 AUC_(0-t),Cmax and Vd between posaconazole suspension and crushed ent eri c-coated tablets after intragastric administration(all P>0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

关 键 词：泊沙康唑 混悬液 肠溶片碾碎 药代动力学 

分 类 号：R978[医药卫生—药品]