Safety Evaluation Of Oxyclozanide

The aim is to evaluate the safety and irritation of the oxyclozanide suspension,provide scientific basis for clinical safe drug use and explore to eliminate or reduce the irritation.This study conducted out a series of safety evaluation tests,for instance,28-day repeated oral toxicity test,eye irritation test,skin irritation test,oral mucosa irritation test and target animal safety test,etc.The purpose of 28-day repeated oral toxicity of oxyclozanide in Wistar rats was to determine toxicity thresholds,target organs,and properties for further study of the toxicity of oxyclozanide.96 Wistar rats were divided into four groups.During the 28 days of the trial,no significant side effects or death were found.The experimental rats showed only mild diarrhea and temporary depression.Significant histopathological changes were observed in the heart,liver,and kidney of rats in the high dose group.There was no significant difference in the results of hematological examination between the treatment groups and the control group.In serum clinical chemistry examination,there were significant differences in ALP,AST,GLU,TBIL,and so on in the high and medium group.After 14 days of reversible recovery observation,the toxic injury indexes except for renal function in the high dose group returned to normal(or there was no significant difference).The results showed that the main toxic target organs of oxyclozanide in a long time(28 days)were liver and kidney,the toxicity of liver and other organs was reversible,and the nephrotoxicity was irreversible within 14 days.The minimum observed adverse effect level(LOAEL)observed was 74 mg/kg.In order to evaluate the irritation of oxyclozanide suspension,toprovide a scientific basis for the safety of clinical administration and to eliminate or alleviate the irritation,eye irritation and skin irritation tests were carried out in rabbits.Left and right autologous controls were used.The results showed that oxyclozanide suspension had no irritation to eyes and skin of rabbits.The irritation of oral mucosa was measured for the first time in oral suspension.This study is to observe the irritation effect of oxyclozanide suspension on oral mucosa and to provide scientific basis for clinical medication.Twenty-four Syrian golden hamsters were divided into 4 groups.Left and right autologous controls were used at 1 h,24 h,48 h,72 h after administration,observation was conducted,and histopathological examination was carried out at the end of the experiment.The results showed that the oral mucosa was very slightly irritated by oxyclozanide suspension.It indicated that illustrated oxyclozanide suspension is safe and reliable in the practical application.The aim of this study was to determine the potential toxicity risk of an oxyclozanide suspension to the target animal,bovine.In this experiment,32 Simmental beef cattle were fattened and fed a full-price diet without antimicrobial agents.The test cattle were divided into 4 groups,which were treated with 0,1,3,and 5 times the recommended dosage through continuous intermittent oral administration at intervals of 2 days.The body weight of the cattle was recorded before and after the experiment,and the weight changes were calculated.The safety of the drugs was evaluated by weight gain,observation of clinical toxicity,hematology,clinical chemistry,and histopathology.The results showed that the cows had different degrees of diarrhea,loss of appetite and depression after administration.The results of clinicopathology had no significant effect.The results of the pathological examination showed that there was a certain degree of damage in the 5 times recommended dose group.The recommended dose was safe to use.Thus,the recommended dose should be given by a single oral administration to ensure the safe use of this drug in the clinic.