Initial Studies On The Toxicology Of Difloxacin Hydrochloride Suspension Emulsions And The Residues In Pigs Tissues

Difloxacin hydrochloride is one of fluoroquinolones used only for veterinary, and shows a broad spectrum and high performance of antimicrobial activity with low toxicity. It can be rapidly absorbed by oral administration, and has long half-life. Suspension emulsions can achieve the effect of target treatment, sustained release and long-acting, which can reduce the drug toxic, side effects and stimulation. In this article, primary study on the toxicity and residue in pig’s tissues of difloxacin hydrochloride suspension emulsions was performed to provide theoretical foundation for its clinical application in veterinary practice.1Study on the toxicity of Difloxacin hydrochloride suspension emulsionsIn order to research the toxicological effects and extent of difloxacin hydrochloride suspension emulsions to target animals,This experiment was designed to investigate acute toxicity, accumulative toxicity, sub-chronic toxicity, mutagenic toxicity and reproductive and developmental toxicity of difloxacin hydrochloride suspension emulsions injection in mice. Acute toxic effect and accumulative toxic effect of difloxacin hydrochloride suspension emulsions injection were detected by modified Kaber method and accumulation coefficient method respectively. The mice were injected with difloxacin hydrochloride suspension emulsions subsequently for28d to evaluate the sub-chronic toxicity. Micronucleus test and sperm structural test of difloxacin hydrochloride suspension emulsions injection were carried out in KM mice to evaluate its mutagenic toxicity. Teratogenicity of SD rats were used for evaluating its reproductive and developmental toxicology. The mouse oral LD50of difloxacin hydrochloride suspension emulsions injection was2303.56mg/kg and the95%confidence interval was2120.41to2502.65mg/kg; LD50arrived at723.89mg/kg after intraperitoneal injection of its suspension and95%confidence interval was678.45mg/kg to772.37mg/kg. The accumulative coefficient(K) was beyond5.26and test group occurred one death. The toxic signs of the mice exposed to high dose that included depression, decreased appetite and poor gain weight in the subchronic toxicity test. The results of blood routine examination and biochemical index of blood indicated that there is no significant different among every group. The results of pathohistology checks indicated that the liver and the kidney was slightly inflamed in high group. The results showed that difloxacin hydrochloride suspension emulsions injection has no muragenic toxicity to KM mice. The results of teratogenicity suggested that difloxacin hydrochloride affected embryo development significantly at the dosage of350mg/kg by causing fetuses dead and skeletal malformation. The severity of the embryo/fetal toxicity has effective relation to the dose. In a conculsion, there is little acute toxicity, no accumulative toxicity of difloxacin hydrochloride suspension emulsions injection, but had some toxicity when administered with a high dosage for a long time.2Study on the residues of difloxacin hydrochloride in swine tissuesWe present a method based on reverse-phase high performance liquid chromatogram for determining residues of difloxacin hydrochloride in swine tissues. The HPLC system consisted of C18column (250mm×4.6mm,5μm) and the mobile phase was2.028g Sodium Dihydrogen Phosphate in1000mL water-acetic acid10mL:Acetonitrile (70:30),and the detection wavelength was280nm. Three concentration levels(20,100,500μg/kg) of difloxacin hydrochloride in the blank tissues were analysed, the recovery of all samples were exceed75%, and the average recovery rates in muscle,liver,kidney,lung and skin+fat was84.72%.80.17%,76.78%.77.90%,79.61%respectively, the intra-day coefficient of variance was betweenl.09%and5.96%, the inter-day coefficient of variance was between1.17%and4.97%. The limit of detection (LOD) of difloxacin hydrochloride in tissues was10μg/kg. The linear ranges of difloxacin hydrochloride sulphate was10-1000μg/kg. Difloxacin hydrochloride was administered intramuscularly to swines at a dosage of5mg/kg,32-day of withdrawal time was recommended.