FATM的代谢产物TMP在兔中的药物代谢动力学行为及组织分布  

Pharmacokinetics and Tissue Distribution of TMP,Metabolite of FATM,in Rabbits

作　　者：童春媚 谭载友[1] 林卓辉[2] 梁绍麟 颜锐思 张晓露[5] 杨慧 黄玉青[1] 陈文菲[1] 黄婷玉[1] 

机构地区：[1]广东药学院,广东广州510006 [2]广东江门市中心医院,广东江门529030 [3]英国伦敦帝国理工学院 [4]广东珠海同益制药有限公司,广东珠海519100 [5]广州医科大学第一附属医院,广东广州510000 [6]诺思格医药科技开发有限公司,北京100048

出　　处：《今日药学》2015年第5期317-320,共4页Pharmacy Today

基　　金：广东省科技研究计划项目(2009B080701025)

摘　　要：目的以阿魏酸2,3,5,6-四甲基吡嗪(FATM)的代谢产物TMP为指标,考察TMP在兔体内的药物代谢动力学特性及其组织分布状况,为日后进一步研究开发FATM的临床应用提供理论依据。方法采用兔灌胃口服给药后的血药浓度经时变化研究TMP。用高效液相色谱-紫外检测器进行样本分析。采用房室模型的药动学软件Kinetica计算TMP的药动学参数。结果 TMP在血液中符合一室吸收动力学模型(权重1/C)。TMP的T1/2α和T1/2β均约为0.27 h;Ka为(2.59±0.25)h-1,Tmax为(0.39±0.02)h,Cmax为(1.81±0.14)μg/m L,AUC为(1.91±0.28)μg·m L-1·h。经检测TMP广泛分布与各器官中,且分布较均匀,浓度最高的脏器为肝,浓度为(0.72±0.02)μg·m L-1·h,其他依次为脾,肾,心,脑,在肺部未能检测出TMP。结论实验数据表明,FATM在兔体内可以迅速吸收,并广泛分布于各组织。FATM是一种有应用前景的潜在药物。OBJECTIVE To investigate the pharmacokinetics and tissue distribution of TMP in rabbits by using TMP,the metabolite of Tetramethylpyrazine ferulate（ FATM）,as the research index. The parameters will be used to design a FATM dosage form for clinical use. METHODS The plasma concentration-time of TMP was observed flowing intragastric administration in rabbits. The samples were determined by a validated high-performance liquid chromatography method. The pharmacokinetic program Kinetica was used to estimate the pharmacokinetics of TMP in rabbits. RESULTS One compartment model was fitted to TMP（ weighting coefficient= 1 / C）. T1 /2αand T1 /2βof TMP were both about 0. 27 h,Ka was（ 2. 59 ± 0. 25） h- 1,Tmaxwas（ 0. 39 ± 0. 02） h,Cmaxwas（ 1. 81 ± 0.14） μg / m L,and AUC was（ 1. 91 ± 0. 28） μg·m L- 1·h. TMP was distributed widely and relatively evenly in tissues assayed. In all the tissues studies,the AUC of TMP in liver was the highest [（ 0. 72 ± 0. 02） μg·m L- 1·h],followed by spleen,kidney,heart and brain,and few TMP was detected in lung. CONCLUSION The experiment data shows,FATM can be absorbed rapidly and distributed widely in those tissues. FATM is a promising candidate of the antithrombotic drug for further development.

关 键 词：FATM TMP 药物代谢动力学 组织分布 

分 类 号：R96[医药卫生—药理学]