title: Dose-linear pharmacokinetics, tissue distribution, and excretion of a recombinant fusion protein 125I-GST-TatdMt possessing potent anti-obesity activity.
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 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.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Kyeonggi-do, 440-746, South Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Chul Hwan
authors.initials: CH
authors.lastname: Kim
authors.forename: Yun Sik
authors.initials: YS
authors.lastname: Jun
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Park
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Yoon
authors.forename: Min-Nyung
authors.initials: MN
authors.lastname: Lee
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: 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*
chemical_list: D015696:Gene Products, tat; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase