童春媚,谭载友,林卓辉,梁绍麟,颜锐思,张晓露,杨慧,黄玉青,陈文菲,黄婷玉
TONG Chunmei,TAN Zaiyou,LIN Zhuohui,LIANG Shaolin,YAN Ruisi,ZHANG Xiaolu,YANG Hui,HUANG Yuqing,CHEN Wenfei,HUANG Tingyu

• 1:广东药学院
• 2:广东江门市中心医院
• 3:英国伦敦帝国理工学院
• 4:广东珠海同益制药有限公司

摘要(Abstract)：

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(KeyWords)： FATM;TMP;药物代谢动力学;组织分布
FATM;TMP;pharmacokinetic;tissue distribution

Abstract:

Keywords:

基金项目(Foundation): 广东省科技研究计划项目(2009B080701025)

作者(Author): 童春媚,谭载友,林卓辉,梁绍麟,颜锐思,张晓露,杨慧,黄玉青,陈文菲,黄婷玉
TONG Chunmei,TAN Zaiyou,LIN Zhuohui,LIANG Shaolin,YAN Ruisi,ZHANG Xiaolu,YANG Hui,HUANG Yuqing,CHEN Wenfei,HUANG Tingyu

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