Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice

作     者：MOO Kai Shing RADHAKRISHNAN Shantini TEOH Magdalene NARAYANAN Prasad BUKHARI Nadeem Irfan SEGARRA Ignacio 

作者机构：Department of Pharmaceutical TechnologySchool of Pharmacy and Health SciencesInternational Medical University(Malaysia) 

出 版 物：《药学学报》 (Acta Pharmaceutica Sinica)

年 卷 期：2010年第45卷第7期

页      面：901-908页

核心收录：

学科分类：0710[理学-生物学] 100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：the International Medical University(IMU)for financial support:Grant#B0104RES(05)2007 

主　　题：imatinib pharmacokinetics liposome tissue distribution 

摘      要：Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of *** assess the pharma-cokinetic and tissue distribution profile of imatinib in a liposome *** single dose(6.25 mg·kg-1) in a liposome formulation was administered iv to male *** concentration was measured in plasma,spleen,liver,kidney and brain using a HPLC ***-compartmental pharmacokinetic approach was used to assess the disposition *** plasma disposition profile was biphasic with a plateau-like second *** AUC0→∞ was 11.24 μg·h·mL-1,the elimination rate constant(kel) was 0.348 h-1 and the elimination half life(t1/2) was 2.0 *** mean residence time(MRT) was 2.59 h,VSS was 1.44 L·kg-1 and clearance was 0.56 L·h·*** achieved the highest tissue exposure:CMAX = 18.72 μg·mL-1;AUC0→∞ = 58.18 μg·h·mL-1 and longest t1/2(4.29 h) and MRT(5.31 h).Kidney and spleen AUC0→∞ were 47.98 μg·h·mL-1 and 23.46 μg·h·mL-1,***-life was 1.83 h for the kidney and 3.37 h for the *** penetrated into the brain reaching ～1 μg·*** correction by organ blood flow the spleen showed the largest uptake *** imatinib presented extensive *** drug uptake kinetics showed mechanism differences amongst the *** findings encourage the development of novel imatinib formulations to treat other cancers.