Study On The Safety And Clinical Curative Effect Of Milbemycin Oxime Pellet To Dogs

The safety evaluation to target animals and clinical curative effect for veterinary drugs are integral parts for drug development process., expressing the traditional toxicity evaluation, adverse effect and curative effect for novel veterinary drugs at single and/or multiple dose adminiatration via animals experiments. Milbemycin oxime belongs to macrolide antibiotic, was isolated from streptomycete broth, was a mixture of milbemycin A3 and A4 oxime derivate, mainly used as exterior and interior anthelminthic in dogs, and is effective to prevent and control dirofilaria immitis infection, and also does well in expelling toxocara canis, ancylostome, whipworm and sarcoptes scabiei, demodicid mite and so on. People focus on it for its high effective and low toxic characters, and it will be used in China in the near future. For the convenient of clinical application, it is necessary to study the safety evaluation and clinical curative effect that's also the reason we do the study here, follows are the main content and results:1) The safety evaluation of milbemycin oxime to dogs 1, 3, 5, 10 times of the clinical administration doses (i.e. 0.5, 1.5, 2.5, 5.0 mg·kg^-1·bw) were chosen to proceed safety evaluation of target animals, the results showed, after administration, only one dog of 10 times clinical dose group showed temporary depression but recovered in 24 h; other animals had no abnormality change in the breath, behavior, spirit, cacation, food consumption body temperature and body weight in experimental stage; the ECG result showed that P, QRS T, U waves and cardiac cycle were normal; the blood routine, liver and kidney function indexes and urine routine were normal; had no influence on blood-serum inorganic salt ion K, Na, Ca, P, Cl; also had no pathological changes on thanatopsy and histopathology check.2) Clinical research of milbemycin oxime Dogs were infected with 100 infective toxocara canis eggs to prepare artificial infected model, and the models were devided into three groups (0.25, 0.5, 1.0 mg·kg^-1·bw,), ivermectin group, positive control group (infected, without treatment) and healthy group (no infection, without treatment). Counted eggs per gram excrement before and after treatment, and counted the worms in intestine after autopsy. The results showed that, there were no eggs in the excrement or worms in the intestine at the end of experiment in the milbemycin oxime group of 0.5, 1.0 mg·kg^-1·bw or ivermectin group, while the results were not so good in the 0.25 mg·kg^-1·bw group.Naturally infected toxocara canis dogs were divided into five groups, they were 0.25, 0.5, 1.0 mg·kg^-1·bw group of milbemycin oxime, ivermectin group, and positive group without treatment. Eggs in the excrement before treatment and 14, 30, 60, 90 days after were recorded in order to conclude the efficiency. There were no eggs since the 14th day after treatment, and there were no worms in the intestine, which showed the perfect helminthicide ability.Healthy dogs of never infected parasite were subcutaneously inoculated by ancylostoma caninum of infective larve to prepare artificial infection model, and then were divided into milbemycin oxime groups (1.0, 0.5, 0.25 mg·kg^-1·bw), positive control group (infected but without treatment), ivermectin group and healthy group (no infection, without treatment). Results showed that the egg reduction rates, helminthicide rates and cure rates of the high-, middle- and low-dose groups of milbemycin oxime and ivermectin group were 100%, 100%, 94.5%, 96.9%; 100%, 100%, 95%, 98%; 100%, 100%, 80%, 80%, respectively, there were no significant difference.Naturally infected ancylostome dogs were divided into five groups, they were 0.25, 0.5, 1.0 mg·kg^-1·bw group of milbemycin oxime, ivermectin group, and positive group without treatment. Eggs in the excrement before treatment and 14, 30, 60, 90 days after were recorded in order to conclude the efficiency. There were no eggs since the 14th day after treatment, and there were no worms in the excrement of high dose group, which showed the perfect helminthicide ability.And the egg reduction rates of the middle- and low-dose groups of milbemycin oxime and ivermectin group were 97.2%, 88.9%, 93.1%. egg darkening rates were 97.5%, 90%, 95%, respectively.Dogs with obviously clinical scabiei symptoms were chosen to be treated with milbemycin oxime of 2.0, 1.0, 0.5 mg·kg^-1·bw, once a week for four weeks, on the 7, 14, 21, 28 days, scraped scurf from five different positions to test sarcoptic mite under microscope, and record the information of scurf, exanthema variolosum, pruritus, trichomadesis according to severity, general and none of every dog, last compute recovery rate. At the end of experiment, the recovery rate of the high dose group was 90%, middle dose group was 86%, low dose group was 70%, ivermectin group was 85%.According to the results, clinical dose schedule was proposed as follows: as to endoparasite, such as toxocara canis and ancylostome, 0.5 mg·kg^-1·bw was needed for oral administration, once a month; and as to exoparasite, such as sarcoptes canis, 2 mg·kg^-1·bw was needed for oral administration, once a week, continually for four weeks.