Recombinant Human Erythropoietin (DWP413)의 적혈구 생성 효과

Hematopoietic Efficacy of Recombinant Human Erythropoietin (DWP413)

  • 최현주 (주)대웅제약 생명과학연구소) ;
  • 김점용 (주)대웅제약 생명과학연구소) ;
  • 임승욱 (주)대웅제약 생명과학연구소) ;
  • 연제덕 (주)대웅제약 생명과학연구소) ;
  • 고여욱 (주)대웅제약 생명과학연구소)
  • 발행 : 2003.06.01

초록

Efficacy and in vivo bioassay of recombinant human erythropoietin (rh-EPO, DWP413) was investigated. Efficacy studies on erythropoiesis were conducted in normal, cisplatin-induced anemic rats and acute hemorrhage - induced anemic rats. Animals were treated intravenously with DWP413 for 5 days, the changes in the number of red blood cells (RBC), hematocrit value (Hct), hemoglobin concentration (Hb) and reticulocyte were examined. In normal rats, at the doses of 50, 250, and 1250 IU/kg/day, in cisplatin-induced anemic rats, at the doses of 50, 100 and 200 IU/kg/day, RBC, Hb, Hct and reticulocyte were increased dose-depen-dently. And in acute hemorrhage-induced anemic rats, DWP413 (150, 450 and 1350 IU/kg/day) significantly increased RBC, Hb, Hct and reticulocytes. In histopathological findings of kidney, cisplatin alone treated rats expressed severe glomerulus and tubular damage. But in the DWP413 treated rats after cisplatin treatment, these were not remarkable compared to cisplatin alone treated rats. In vivo bioassay, DWP413 had 102.43% of bioactivity compared to erythropoietin BRP(Biological Reference Product, European Directorate for the Quality of Medicines). These results suggest that DWP413 might be useful for the therapy of anemia induce by renal failure and acute blood loss.

키워드

참고문헌

  1. Anagnostou, A. (1985). Erythropoietin: a hematopoietic hormone produced by the kidney. Semin. Nephrol. S, 104-114
  2. Edward A., Levine, M.D., Arthur L., Rosen, Ph. D., Laksman R., Sehgal, Ph. D., Steven A., Gould, M.D., Joan C., Eglie, Ph. D., Ransa L., Sehgal, B.S.M.T., and Gerald S.Moss. M.D. (1989). Treatment of acute postoperative anemia with recombinant human erythropoietin. J.Trauma, 29, 1134-1139 https://doi.org/10.1097/00005373-198908000-00011
  3. Emest B., Marshall A.L., Barry S.C., Thoman J.K. (ed.)(1995). Williams Hematology pp.704-708. McGraw-Hill, New York
  4. Fuchs, A. and Eder, H. (1992). Dose dependenl effects of recombinant human erythropoietin on tile reticulocyte population of rabbits. Arzeim.-Forsch./Drug. Res. 42. 10, 1266-1268
  5. Jacobs, K, Shoemaker, C., Rudersdorf, R., Neill, S. D., Kaufman, R. J, Mufson, A, Seelu'a, J., jones, S. S., Hewick, R, Fritsch, E. E, Kawakita, M., Shimizu, T and Miyake, T. (1985). Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature 313, 806-810. https://doi.org/10.1038/313806a0
  6. Joseph, W E. and John, W A (1989). Guideline for recombinant human erythropoietin therapy. Am. J. Kidney Dis. 2, 2-8
  7. Kim D., H., Ahn B. O., Park J. H., Lee S. H., and Kim W. B. (1998). Efficacy of recombinant human erythropoietin (rhuEPO). J. Appl. Pharmacol. 6,312-316
  8. Kim S. J., Ha B. J, Lee D. E., Oh M. S., Kim D. H., Park K. H. and Kim H. S. (1994). Efficacy of recombinant erythropoietin from CHO cells. J. Appl. Phamiacol. 2, 343-346
  9. Kuzur M. E. and Greco F. A. (1980). Cisplatin induced anemia. New Engl. J. Med. 303, 110-112
  10. Landschulz K. T., Boyer S. H., Noyes A. n, Rogers O. C, and Frelin L. P. (1992). Onset of erythropoietin response in murine erythroid colony forming units: assignment to early S-phasc in a specific cell generation. Blood, 79, 2749-2758
  11. Levine E. A, Rosen A. L., Sehgal L. R., Gould S. A, Egrie j. C, Sehgal H. L and Moss G. S. (1989). Treatment of acute postoperative anemia with recombinant human erythropoietin, J. Trauma 29, 1134-1139 https://doi.org/10.1097/00005373-198908000-00011
  12. Masunaga, H., Goto, M. and Ueda, M. (1986). Effects of purified erythropoietin in partially nephrectomized rats. Acta Hematol. Jpn. 49, 807-815
  13. Masunaga, H., Takahira, Rand Sawai, T. (1991). Effects of recombinant human erythropoietin on renal anemic rats induced by drugs. Folia. Pharmacol. Jpn. 98, 151-160 https://doi.org/10.1254/fpj.98.2_151
  14. McGonigle R. J., Brookins J, Pegram B. L. Fisher J.W (1987) : Enhanced erythropoietin production by calcium entry blockers in rats exposed to hypoxia. J. Pharmacol. Exp. Then 241, 428-432
  15. Nam C. J., Kim H., Huh J. W, Kang J. K. (1989). Efficacy of recombinant human erythropoietin. Korean J. of the Lab. Anim. Sci. 14, 241-249
  16. Nathan D. G., Syikowski A. (1983). Erythropoietin nd the regulation of erythropoiesis. N Engl. J. Med. 306, 520-522
  17. Palmeri S., Russo A., Gebbia V, Borsellino N., Gebbia N., Rustum Y., Rausa L. (1990). A phase I-II study on the toxicity and therapeutic efficacy of 5-fluorouracil in cornbinatjion with leucovorin and cisplatin in patients with advanced colorectal carcinoma. J. Chemotherapy suppl. I, 28-32
  18. Ridley, D. M., Dawkins, F. and perlin, E. (1994). Erythropoietin : A review. J. Natl. Med. Assoc. 86, 129-135
  19. Roberta L. Scipioni, Richard W. Diters, William R. Myers, and Susan M. Hart. Clinical and clinicopathological assessment of serial phlebotomy in the Sprague Dawley rat. Laboratory Ani. Sci. 1997. 47, 293-299
  20. Rossof, A. H., Slayton, R. E. and Pcrlia, C. P. (1972). Preliminary clinical experience with cisdiamminedichloroplatinum (II). Cancer 30, 1451-1450 https://doi.org/10.1002/1097-0142(197212)30:6<1451::AID-CNCR2820300606>3.0.CO;2-Q
  21. Rathmann S. A. and Wcik J. K. (1981). Cisplatin-induced anemia. New. Eng. J. Med. 303, 110-112.
  22. Rothmann, S. A., Paul P., Weick, J. K., Mclntyre, W. R. and Fantelli. F. (1985). Effects of cis-diamminedichloroplatinum on erythropoietin production and hematopoietic progenitor cells. Int. J. Cell Cloning 3, 415-423 https://doi.org/10.1002/stem.5530030607
  23. Tsuda, E., Goto, M., murakarni, A, Akai, K., Ueda, M., Kawanishi, G., Takakashi, N., Sasaki, R., Chiba, H., ishihara, H., Mori, M., Tejima, S., Endo, S. and Arata, Y. (1988). Comparative structural study of N-linked oligosaccharides of urinary and recombinant eryihropoietins. Biochemistry 27, 5646-5654 https://doi.org/10.1021/bi00415a038
  24. Vaziri N. D., ZhoLl X. J., and Liao S. Y. (1994). Erythropoietin enhances recorvery from cisplatin-induccd acute renal failure. Am. J. Physiol. 266(Renal Fluid Electrolyte Physiol 35): F360-F366 https://doi.org/10.1152/ajpcell.1994.266.2.C360
  25. Wood, P. A. and Hrushesky, W. J. M. (1995). Cisplatinassociated anemia; an erythropoietin deficiency syndrome. J. Clin. Invest. Inc. 95, 1650-1659 https://doi.org/10.1172/JCI117840