Pharmacokinetics of GST-TatdMt, a recombinant fusion protein possessing potent anti-obesity activity, in mice.
This study examined the absorption and pharmacokinetic disposition of 125I-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 radioiodinated 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 microg). Upon i.v. injection, the average terminal elimination half-life (t1/2,lambdaz), AUC and AUMC were 6.4 h, 318.2 nCixh/mL and 2518 nCixh2/ mL, respectively. The highest radioactivity was observed in lung followed by liver, spleen, heart and kidney. The t1/2lambdaz values obtained from i.v., i.p., and oral administration were comparable from each other (range 5.8-6.4 h). The absolute bioavailability of 125I-GST-TatdMt was 42.8% and 60.5% after p.o. and i.p. administration, respectively. Given the cell-penetrating nature, 125I-GST-TatdMt may be absorbed into the systemic circulation to a relatively high extent after extravascular administration.
Shin
Beom Soo
BS
College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, 712-702, Korea.
Seo
Jin Hyuk
JH
Hur
Man-Wook
MW
Lee
Min-Nyung
MN
Yoo
Sun Dong
SD
D000818:Animals; D019440:Anti-Obesity Agents / Q000493:pharmacokinetics*; D015696:Gene Products, tat / Q000493:pharmacokinetics*; D005982:Glutathione Transferase / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D019440:Anti-Obesity Agents; D015696:Gene Products, tat; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase