Abstract

THE PHARMACOKINETICS AND TISSUE DISTRIBUTION OF FATM, A NOVEL ANTITHROMBOTIC AGENT, FOLLOWING ORAL ADMINISTRATION IN RABBITS

Chunmei Tong, Zaiyou Tan*, Zhuohui Lin, Shaolin Liang, Ruisi Yan, Xiaolu Zhang, Hui Yang, Yuqing Huang, Wenfei Chen and Tingyu Huang.

ABSTRACT

Background: FATM Tetramethylpyrazine ferulate a novel antithrombotic medicine was investigated in rabbits and pharmacokinetics and tissue distribution were observed. The parameters will be used to design a FATM dosage form for clinical use. Methods: The pharmacokinetic and tissue distribution of FATM was studied following oral administration in rabbits. A High Performance Liquid Chromatography system with UV detection was developed for the analysis of the samples. A compartment method of a pharmacokinetic program Kinetica were used to estimate the pharmacokinetic of FATM in rabbits. Results: The results showed a two compartment model was fitted to FATM (weighting coefficient = 1/c2). T1/2α of FATM was 0.49 h, T1/2βwas 1.84 h, Ka was 6.04 h-1, Tmax was 0.35 h, Cmax was 18.69 μg /mL, and AUC was 36.05 μg*h*mL-1. FATM was distributed widely in tissues assayed. In all the tissues studies, the AUC of FATM in kidney was the highest (31.9 mg/L*h), and in brain was the lowest (1.27 mg/L*h). Conclusion: To sum up the present observations, it indicated FATM can be absorbed rapidly and concentrate in those organs which well perfuse with blood, showing that it is a promising candidate of the antithrombotic drug for further development.

Keywords: FATM, pharmacokinetic, tissue distribution, compartment model.