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Letters in Drug Design & Discovery
ISSN (Print): 1570-1808
ISSN (Online): 1875-628X
Epub Full Text Article
DOI: 10.2174/1570180811666140121234608      Price:  $95

Pharmacokinetic Analysis of Tetramethylpyrazine Bis-Nitrone TN-2 in Rats and its Protein Binding In Vitro

Author(s): Yewei Sun, Kaiyi Liao, Sai Li, Zaijun Zhang, Pei Yu and Yuqiang Wang
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.
Pharmacokinetics, Tissue distribution, Excretion, Plasma protein binding, Bioavailability, 2, 5-[[(1, 1-Dimethylethyl) oxidoimino]methyl]-3, 6-trimethylpyrazine
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.