In vivo and In vitro Metabolism of Recombinant Human Epidermal Growth Factor (DWP401) in Rats

재조합 인간 상피세포성장인자(DWP401)의 흰쥐에서의 in vivo와 in vitro 대사

  • 고여욱 ((주)대웅제약 중앙연구소) ;
  • 남권호 ((주)대웅제약 중앙연구소) ;
  • 정주영 ((주)대웅제약 중앙연구소) ;
  • 박승국 ((주)대웅제약 중앙연구소) ;
  • 유영효 ((주)대웅제약 중앙연구소) ;
  • 김재환 ((주)대웅제약 중앙연구소) ;
  • 한건 (충북대학교 약학대학) ;
  • 박명환 ((주)대웅제약 중앙연구소) ;
  • 심창구 (서울대학교 약학대학)
  • Published : 1997.06.01

Abstract

Metabolism of DWP401, recombinant juman epidermal growth factor, was examined in vivo and in vitro in rats. When $^{125}I$-labeled DWP401 was administered at a dose of 50 ${\mu}g$/kg by i.v. injection. $^{125}I$-labeled DWP401 was rapidly degraded within 30 minytes above 93%. Thin layer chromatography analysis of urine collected for 24 hr after i.v. administration of $^{125}I$-labeled DWP401 showed ohly one spot on a X-ray film which was considered as diiodo-tyrosine. This result suggests tha $^{125}I$-labeled DWP401 was completely digested into free amino acids without any specific intermediate polypeptides. About 42.1% of the administered iodine was recovered in 24 hr. For in vitro degradation study, $^{125}I$-labeled DWP401 was added to plama and tissue homogenates of rats and incubated at $37^{\circ}C$. Almost 98% of the added radioactivity recovered from the protein fraction of the liver, kidey, small intestine, stomach and spleen decreased rapidly. For examplem the recovery rates of $^{125}I$-labeled DWP401 were 58.6, 63.2, 39.9, 52.9 and 66.8% after 4hrs of incubation in respective organ homogenates.

Keywords

References

  1. J. Biol. Chem. v.237 Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal Cohen, S.
  2. J. Biol. Chem. v.248 Epidermal growth factor location of disulfide bond Savage, C. R.;Hash, J. H.;Cohen, S.
  3. J. Biol. Chem. v.247 The primary structure of epidermal growth factor Savage, C. R.;Inagami, T.;Cohen, S.
  4. J. Invest. Dermatol. v.40 The stimulation of epidermal keratinization by a protein isolated from the submaxillary gland of the mouse Cohen, S.;Elliot, G. A.
  5. J. Sug. Res. v.33 The effect of epidermal growth factor on wound healing in mice Nill, M.;Ryan, G. B.;O'Brien, B. M.
  6. N. Engl. J. Med. v.321 Enhancement of wound healing by topical treatment with epidermal growth factor Rown, G. L.;Nanney, L. B.;Griffen, J.
  7. J. Exp. Med. v.163 Enhancement of epidermal regeneration by biosynthetic epidermal growth factor Brown, G. L.;Curtsinger, L.;Brightwell, J. R.
  8. J. Clin. Gastroenterol v.10 no.suppl. 1 Experimental and clinical studies on epidermal growth factor for gastric mucosal protection and healing of gastric ulcers Itoh, M.;Joh, T.;Imai, S.;Miyamato, T.;Matsusako, K.;Iwai, A.;Katsumi, K.;Endo, K.;Takeuchi, T.
  9. Regulatory Peptide v.23 Distribution of i.v. administered epidermal growh factor in the rat Jorgensen, P. E.;Poulsen, S. S.;Nexo, E.
  10. Int. J. Pharm. v.49 Biliary and urinary excretions of immunoreactive human epidermal growth factor after intravenous administration in rats Murakami, T.;Kishimoto, T.;Higashi, Y.;Amagase, H.;Hayashi, T.;Fuwa, T.;Yata, K.
  11. J. Cell. Biol. v.98 Receptor mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: Ligand and receptor dynamics Dunn, W. A.;Hubbard, A. L.
  12. Biochem. Pharm. v.38 no.12 Kinetic analysis of the elimination process of human epidermal growth factor(hEGF) in rats Kim, D. C.;Sugiyama, Y.;Fuwa, T.;Sakamoto, S.;Iga, T.;Hanano, M.