Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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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, Yuqiang Wang.

Graphical Abstract:


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.

Keywords: Pharmacokinetics, Tissue distribution, Excretion, Plasma protein binding, Bioavailability, 2, 5-[[(1, 1-Dimethylethyl) oxidoimino]methyl]-3, 6-trimethylpyrazine.

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Article Details

VOLUME: 11
ISSUE: 6
Year: 2014
Page: [770 - 777]
Pages: 8
DOI: 10.2174/1570180811666140121234608
Price: $58