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Dose-linear pharmacokinetics, tissue distribution, and excretion of a recombinant fusion protein 125I-GST-TatdMt possessing potent anti-obesity activity

Authors
 Beom Soo Shin  ;  Chul Hwan Kim  ;  Yun Sik Jun  ;  Eun Hye Park  ;  Man-Wook Hur  ;  Kang Choon Lee  ;  Yu Seok Yoon  ;  Min-Nyung Lee  ;  Sun Dong Yoo 
Citation
 REGULATORY PEPTIDES, Vol.129(1) : 25-30, 2005 
Journal Title
 REGULATORY PEPTIDES 
ISSN
 0167-0115 
Issue Date
2005
MeSH
Animals ; Gene Products, tat/administration & dosage ; Gene Products, tat/genetics ; Gene Products, tat/pharmacokinetics* ; Glutathione Transferase/administration & dosage ; Glutathione Transferase/genetics ; Glutathione Transferase/pharmacokinetics* ; Injections, Intravenous ; Iodine Radioisotopes/administration & dosage ; Iodine Radioisotopes/pharmacokinetics ; Male ; Obesity/drug therapy* ; Obesity/metabolism ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/administration & dosage ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/pharmacokinetics*
Keywords
Tat ; GST-TatdMt ; Obesity ; Pharmacokinetics ; Tissue distribution
Abstract
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 μg (1640 nCi), 18 μg (3388 nCi), and 35 μg (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 AUCINF (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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0167011505000224
DOI
10.1016/j.regpep.2005.01.010
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/150032
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