• Toxicological Research
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• 제22권1호
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• pp.61-67
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• 2006

Changes in hematology and serum biochemistry after treatment of recombinant human erythropoietin (rHuEPO, HM10760) were screened in 4 male cynomolgus monkeys (Macaca fascicularis). Four monkeys, composed of a treatment group of HM10760 and a positive control group of $Aranesp^(R}$, were subcutaneously administered at same dose of $100{\mu}g/kg$. Both groups did not show any change in body weights and food consumption for 4 weeks compared with those of pretreatment. Both groups did not show any change in total leukocyte count (WBC) and platelet count, while both groups showed increased platelet distribution width (PDW) percentage in HM10760 group during a period from day 5 to day 59 and in $Aranesp^(R}$ group during a period from day 9 to day 26. Both groups showed increases in red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT) approximately 10 days after treatment compared with those of pretreatment (day 0). The increased levels of RBC, HGB, and HCT were much higher in HM10760 than in $Aranesp^(R}$ by the increases of $3.2%{\sim}12.5%$ for RBC, $3.8%{\sim}17.1%$ for HCT, and $1.85%{\sim}11%$ for HGB. Both groups showed increases in red cells distribution width (RDW) and reticulocyte (RET) compared with those of pretreatment, showing the highest peak from day 9. The increased level of RET lasted up to day 14 in $Aranesp^(R}$ group, while it lasted up to day 23 in HM10760 group. The increased level of RDW lasted up to day 59, it was much higher in HM10760 by the increase of $10.1%{\sim}17.6%$ than in $Aranesp^(R}$ group. In serum biochemistry, both groups showed a decrease in chloride level compared with those of pretreatment. These findings indicated that HM10760 increased RBC, HGB, HCT, RDW, and RET compared with those of pretreatment, and the increased levels were much higher in HM10760 than in $Aranesp^(R}$.

• Toxicological Research
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• 제21권3호
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• pp.241-247
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• 2005

HM10760 is a recombinant human erythropoietin that has beer developed as a drug for anemia. In this study, antigenic potential of HM10760 was examined by active systemic anaphylaxis in guinea pigs and passive cutaneous anaphylaxis in a guinea pig-guinea pig system. HM10760 was subcutaneously administered at 0, 2, and $20{\mu}g/kg$ and also as a suspension with adjuvant ($20{\mu}g/kg$ + FCA). Ovalbumin as a suspension with adjuvant was administered to induce positive control responses. In the active systemic anaphylaxis test, no symptoms except rubbing or licking nose and urination that were considered as physiological phenomena were observed at $0{\mu}g/kg$. Four of 5 animals at $2{\mu}g/kg$ and all the 5 animals at $20{\mu}g/kg$ showed cyanosis and lying on side. All animals in the adjuvant mixture group showed relatively mild symptoms such as rubbing or licking nose, urination, and evacuation. In the passive cutaneous anaphylaxis test, 0/5, 3/5, and 5/5 serum samples from the animals immunized with 0, 2, and $20{\mu}g/kg$, respectively, showed positive reactions against HM10760. All 5 sera collected from the animals immunized with an adjuvant mixture contained HM10760-specific antibodies. These results suggest HM10760 have antigenicity in guinea pigs.