Intravenous Single Dose and Four-week Repented Dose Toxicity Study of YHB216, a Recombinant Human Erythropoietin, in Beagle Dogs

YHB216의 비글개에서 정맥내 단회 및 4주 반복투여독성시험

  • 노용우 (충북대학교 수의과대학) ;
  • 장호송 (충북대학교 수의과대학) ;
  • 지형진 (충북대학교 수의과대학) ;
  • 정은용 (충북대학교 수의과대학) ;
  • 신지순 (충북대학교 수의과대학) ;
  • 강민정 ((주)유한양행 중앙연구소) ;
  • 안경규 ((주)유한양행 중앙연구소) ;
  • 최연식 ((주)유한양행 중앙연구소) ;
  • 이종욱 ((주)유한양행 중앙연구소)
  • Published : 2002.03.01


Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/kg to dogs (2 dogs/sex/group). There were no treament-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500IU/kg (3 dogs/sex/group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/kg or more. These changes are all considered to be Pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD50 value was above 25,000 IU/kg in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/kg day in the repeated dose toxicity study of YHB216 in dogs.



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