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.
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.