Study On The Safety Toxiclogy Of Gentamicin-Lincomycin Injection

The safety evaluation for veterinary drugs is an integral part for drug development process. It is the traditional toxicity evaluation for new veterinary drugs at single and/or multiple dose adminiatration via animals experiments. Gentamicin—Lincomycin injection is a newly studied drug against streptococcus suis. In this study, tests of the general toxicity, target animal safety and cell toxicity were taken to provide a theoretical and experimental basis for using it in clinical safety and rational dose.LD50 of Gentamicin—Lincomycin injection by intramuscrular adminstration in mice, was 4.989 ml/kg (ie 0.399g/kg), equivalent to 15 times of the clinical dose, showing that its acute toxicity was less.Irritant tests included the experimental hemolysis, muscle stimulation, vascular irritation test and skin irritation test in rabbits , the general and allergic skin allergy tests in guinea-pigs. The results were as follows: Hemolysis or coacervation in the red blood cells in rabbts did not occur for 0.1～0.5mL of the injection in 4h; Pathological changs such as hyperaemia, edema or hemorrhage were not examined in the veins where they were injected intravenousiy and in their surrounding tissues, hyperaemia occurred ranged below 0.5cm×1.0cm on the intramuscular injection site, the difference value between the maximum and the minimum order of reaction in quadriceps was zero moreover the sum of them was less than 10; Double dose of the clinical doage of the injection was smeared on the rabbit skin, obvious pathological changes were not observed after the drug withdrawal for 1h,24h,48h and 72h; Anaphylactic reaction was not observed in the guinea pigs after they were first sensibilized for 14 and 21d.In the target animal safety experiments, piglets were administrated at 1, 3, 5 times of the clinical dose of Gentamicin—Lincomycin injection for seven days, once a day. The clinical symptoms were observed, the hematological and functional parameters of liver and kidney were determined in each group. Then pathological anatomy and histology examination of the piglets were carried out. The results showed that, the drugs had no effect on the growth of piglets, and there were no significant differences in the indicators of the blood and liver. With the increasing of the injection concentration, renal functional indicatrixes had significant differences among all treatmental groups.In order to evaluate the toxicity of Gentamicin—Lincomycin injection on cells, PK-15 cells were treated with it (0.2-3.2mg/mL) for 24～72h. Its effect of growth inhibition on cells was measured by 3-(4,5dimethylthiazol)-2,5-diphenyltetrazoliumbromide (MTT). The determination of leakage of LDH and NAG was performed using a commercial kit. The results showed that the Gentamicin—Lincomycin injection inhibited the growth of PK-15 cells, and moreover, the inhibition increased linearly with the increase of the injection concentrations and times of incubation, Namely, as its concentration increased, LDH or NAG leakage also increased. It is concluded that the Gentamicin and Lincomycin injection exerted certain toxicity on cells.