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

Abstract

This study examined the absorption and pharmacokinetic disposition of I-125-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. I-125-GST-TatdMt was administered to mice by i.v., i.p. and oral administration at doses of 652.7 nCi (102.3 tg). Upon i.v. injection, the average terminal elimination half-life (t(1/2,lambda z)), AUC and AUMC were 6.4 h, 318.2 nCi center dot h/mL and 2518 nCi center dot h(2)/ mL, respectively. The highest radioactivity was observed in lung followed by liver, spleen, heart and kidney. The t(1/2,lambda z) 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 I-125-GST-TatdMt was 42.8% and 60.5% after p.o. and i.p. administration, respectively. Given the cell-penetrating nature, I-125-GST-TatdMt may be absorbed into the systemic circulation to a relatively high extent after extravascular administration.