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Pharmacokinetics of GST-TatdMt, a recombinant fusion protein possessing potent anti-obesity activity, in Mice

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Abstract

This study examined the absorption and pharmacokinetic disposition of125l-GST-TatdMt, a recombinant Tat protein possessing potent anti-obesity activity, in mice after vascular and extravascular administration. GST-TatdMt was over-expressed in E. coli, purified, and radio-iodinated using the IODO-GEN method.125I-GST-TatdMt was administered to mice by i.v., i.p. and oral administration at doses of 652.7 nCi (102.3 μg). Upon i.v. injection, the average terminal elimination half-life (t1/2,λz), AUC and AUMC were 6.4 h, 318.2 nCi·h/mL and 2518 nCi·h2/ mL, respectively. The highest radioactivity was observed in lung followed by liver, spleen, heart and kidney. The t1/2,λz values obtained from i.v., i.p., and oral administration were comparable from each other (range 5.8–6.4 h). The absolute bioavailability of125I-GST-TatdMt was 42.8% and 60.5% after p.o. and i.p. administration, respectively. Given the cell-penetrating nature,125l-GST-TatdMt may be absorbed into the systemic circulation to a relatively high extent after extravascular administration.

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Correspondence to Beom Soo Shin or Jin Hyuk Seo or Man-Wook Hur or Min-Nyung Lee or Sun Dong Yoo.

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Shin, B.S., Seo, J.H., Hur, M. et al. Pharmacokinetics of GST-TatdMt, a recombinant fusion protein possessing potent anti-obesity activity, in Mice. Arch Pharm Res 30, 1162–1167 (2007). https://doi.org/10.1007/BF02980253

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Key words

  • Tat
  • Pharmacokinetics
  • Bioavailability
  • Distribution
  • Obesity