Title:Pharmacokinetic Analysis of Tetramethylpyrazine Bis-Nitrone TN-2 in Rats and its Protein Binding In Vitro
VOLUME: 11 ISSUE: 6
Author(s):Yewei Sun, Kaiyi Liao, Sai Li, Zaijun Zhang, Pei Yu and Yuqiang Wang
Affiliation:Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou, 510632, China.
Keywords:Pharmacokinetics, Tissue distribution, Excretion, Plasma protein binding, Bioavailability, 2, 5-[[(1, 1-Dimethylethyl)
oxidoimino]methyl]-3, 6-trimethylpyrazine.
Abstract:2,5-[[(1,1-Dimethylethyl)oxidoimino]methyl]-3,6-trimethylpyrazine (TN-2), a novel derivative of tetramethylpyrazine
(TMP), is effective in reducing brain infarct size in animal brain ischemia models. The purpose of this study is to
evaluate its pharmacokinetic profiles including plasma pharmacokinetics, dose proportionality, tissue distribution, excretion
in rats and protein binding ability in vitro. In doses ranging from 5 to 80 mg/kg, TN-2 displayed linear pharmacokinetic
characteristics. After intragastric (i.g.) administration, it was absorbed rapidly and the maximum concentration
(Cmax) was observed at 28.5 min. The absolute bioavailability was 69.3%. After intravenous (i.v.) injection, TN-2 distributed
to various tissues rapidly. The area under curve (AUC) of TN-2 in brain tissues was 14% in plasma. Kidney was
the main excretory organ where approximately 80% was excreted in the prototype form through urine. The protein binding
rate was 3.4% and 12.5%, respectively, in plasma of rat and human.
