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Pharmacokinetics of 125I-GST-TatdMt, a recombinant fusion protein possessing potent anti-obesity activity, after intravenous, nasal, oral, and subcutaneous administration

 Beom Soo Shin  ;  Chul Hwan Kim  ;  Min-Nyung Lee  ;  Man-Wook Hur  ;  Kang Choon Lee  ;  Yu Seok Youn  ;  Sun Dong Yoo 
 REGULATORY PEPTIDES, Vol.140(1~2) : 74-80, 2007-04 
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Issue Date
Administration, Intranasal ; Administration, Oral ; 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 ; Injections, Subcutaneous ; Iodine Radioisotopes ; Male ; Obesity / drug therapy* ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins / administration & dosage ; Recombinant Fusion Proteins / genetics ; Recombinant Fusion Proteins / pharmacokinetics* ; Time Factors ; Tissue Distribution
This study first reports the absorption kinetics of GST-TatdMt, a recombinant Tat protein possessing potent anti-obesity activity, in rats after nasal, s.c., and p.o. administration. 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 by nasal, s.c., and oral routes at doses of 7.3 microg (420.7 nCi), 146.5 microg (8413.8 nCi), and 146.5 microg (8413.8 nCi), respectively. For the determination of absolute bioavailability, 125I-GST-TatdMt was also given to rats by i.v. injection (73.2 microg, 4206.9 nCi). Following administration by extravascular routes, the systemic absorption of radioactivity was prolonged, with Cmax being attained within 4.2-8.0 h. The absolute bioavailability calculated as dose-normalized AUC(extravascular)/AUC(i.v.) was 98.0, 75.8, and 87.1% after nasal, s.c., and oral administration, respectively. The majority of administered radioactivity was excreted in urine (57.5-64.7%), with fecal excretion being less (2.5-12.7%). The distribution of 125I-GST-TatdMt to various tissues was also determined at 4 and 72 h after s.c. injection. The findings of this study suggest that this protein may be absorbed into the systemic circulation when given by extravascular administration.
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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
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