The Chronic Toxicity Experiment Of Pegylated Consensus Interferon

Objective: To study the chronic toxicity of pegylated consensus interferon,make sure the target organs for toxicity,provide the no-observed-adverse-effect level(NOAEL)of cynomolgus monkey,and designed to provide reference for the safety dose of people.Methods: There are 24 cynomolgus monkeys were used for this study with half females and half males,the female's weight were between 2.81~3.25 kg,and the male's weight were between 3.26~3.96 kg.The animals were divided randomly into 4 groups: 3 females and 3 males per group,a low dose group of 15?g/kg·BW PEG-cIFN,a middle dose group of 45?g/kg·BW PEG-cIFN,a high dose group of 150?g/kg·BW PEG-cIFN and a vehicle control group.Dose for 14 weeks by subcutaneous injections once a weekly.Results: Compared with the control group,the activities,feces,injection site,weight,electrocardiogram,blood biochemistry and urine of low(15?g/kg·BW),middle(45?g/kg·BW),and high(150?g/kg·BW)dose groups have no significant difference.On day 16,the RBC?HGB?HCT of high dose group were lower than control group,the difference was significant,but the hematological index of other does groups have no significant difference compared with control group.And the obvious pathological changes has been found in two animals(50%)of high dose group,which were the number of mesangial cell in kidney was increased,mesangial matrix was hyperplasia and lumen of capillary was narrow.All of the pathological changes basically recovered to normal after stopping injection for 60 days.Conclusion: For the high(150?g/kg·BW)dose group,the transien reduce of red cell indexes has been found in the early dose phase,and the number of mesangial cell in kidney was increased,mesangial matrix was hyperplasia and lumen of capillary was narrow have been found in two animals via pathological examination.And for the low(15?g/kg·BW)and middle(45?g/kg·BW)groups,no significant toxicity has been found.In this study,the NOAEL of cynomolgus monkey is 45?g/kg·BW,which is about 18 times of the clinical dosage in humans.