Dose-linear pharmacokinetics, tissue distribution, and excretion of a recombinant fusion protein 125I-GST-TatdMt possessing potent anti-obesity activity.
This study first examined the pharmacokinetic disposition of GST-TatdMt, a recombinant Tat protein possessing potent anti-obesity activity, in rats after i.v. injection. GST-TatdMt was over-expressed in E. coli, purified, and radioiodinated using the IODO-GEN method. The radioiodinated 125I-GST-TatdMt was administered to rats at doses of 9 microg (1640 nCi), 18 mug (3388 nCi), and 35 microg (6420 nCi). Upon administration, the total radioactivity in serum declined bi-exponentially, with the average terminal elimination half-life ranging from 13.7 to 15.7 h. There was a linear relationship between dose and AUC(INF) (r2=1.000) and between dose and Co (r2=0.999). The fraction of administered radioactivity excreted in feces was low (mean range 1.5-2.8%), while the majority of the radioactivity was excreted in urine (mean range 54.9-61.4%). The radioactivity found in the liver, lungs, spleen, and kidneys were higher than in serum, but the tissue-to-serum ratios were relatively low (<1.64). The radioactivity in testes, adipose tissue, heart, and brain was lower than in serum (tissue-to-serum ratios 0.046-0.27). The findings of this study indicate dose-linear pharmacokinetics of 125I-GST-TatdMt in rats over the i.v. dose range studied.
Shin
Beom Soo
BS
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Kyeonggi-do, 440-746, South Korea.
Kim
Chul Hwan
CH
Jun
Yun Sik
YS
Park
Eun Hye
EH
Hur
Man-Wook
MW
Lee
Kang Choon
KC
Yoon
Yu Seok
YS
Lee
Min-Nyung
MN
Yoo
Sun Dong
SD
D000818:Animals; D015696:Gene Products, tat / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D005982:Glutathione Transferase / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*
D015696:Gene Products, tat; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase