Preliminary Study On Safety And Clinical Outcomes Of Halofuginone Hydrobromide

Halofuginone hydrobromide is a halogenated analogue of the dichroin B which found in the roots and leaves of the Chinese medicinal plant Dichroa febrifuga(also called Chinese quinine)belonging to the quinazoline derivatives,having efficient anticoccidial activity,and with no cross-resistance for other coccidiostats.Halofuginone hydrobromide was added to feed for the prevention and cure of coccidiosis,the recommended dose is 3 mg·kg-1.To provide reference for rational application clinically,this issue carried out the preclinical safety study of the halofuginone hydrobromide APIs and premix.Details were as follows:1.The acute toxicity study of halofuginone hydrobromideIn order to evaluate the acute oral toxicity of the halofuginone hydrobromide,observed toxic reaction,reveal the possible toxic effects of target organs,and provide the reference for the clinical application.This study used the modified Karber’s mehod,SD rats were used as experimental animal,oral acute study to obtain the LD50 and 95%confidence intervals of halofuginone hydrobromide.The results showed that the oral LD50 values of halofuginone hydrobromide to be 12.53 mg·kg-1 body weight and the approximate 95%confidence interval ranging from 8.93 to 17.59 mg·kg-1 body weight in rats.In conclusion,according to the classification table of chemical acute toxicity,halofuginone hydrobromide was classified as a high-toxic substance.2.The safety-study on target speciesIn order to evaluate the safety of halofuginone hydrobromide in chickens,to understand its effective dose,recommended dose and toxic dose on the target animal pathological,physiological and biochemical changes,and provide the reference for the clinical application.This study referred to the VICH guideline "Target animals safety for veterinary pharmaceutical",chickens were provided with halofuginone hydrobromide for 42 days and the body weight gains,bloody and seum component was measured.The results showed that there was no statistical difference about the parameters between each group.No obvious unnormal syndrome was observed after autopsy and histological examination.In conclusion,it’s prorosed halofuginone hydrobromide(3 mg·kg-1)was safe to use as a coccidiostat.3.The anticoccidial effect evaluation of halofuginone hydrobromideIn order to evaluate the anticoccidial efficacy of halofuginone hydrobromide,provide the reference for Phase Ⅲ clinical trial and application.This study selected healthy chickens,set blank control group,positive control group,high dose group(6 mg·kg-1),middle dose group(3 mg·kg-1),low dose group(1.5 mg·kg-1)and maduramicin ammonium control group(5 mg·kg-1).At age of 20 days inoculate of Eimeria tenella orally.Calculation the ACI and determined the efficacy at the end of the test.The results showed that the anticoccodial index(ACI)of halofuginone hydrobromide recommended dose(3 mg·kg-1)was 184.92.In conclusion,Halofuginone hydrobromide was a good coccidiostat.