Pharmacokinetic Analysis Of Nano-ivermectin Pouring Agent And Its Clinical Effect In Dogs

Ivermectin is semi-synthetic macrocyclic lipid anthelmintic drug produced by streptomyces avermitilis,which has advantageous characteristics like broad spectrum,high efficiency,safety,low dose and no cross resistance.Ivermectin has been widely used in the control and protect of canine gastrointestinal nematodes,pulmonary nematodes and parasitic arthropods in cattle,sheep,horses and pigs.The form of the ivermectin on the veterinary drug markets includes premixes,tablets,oral solutions,injections,pouring agents and others.Clinical trials show that oral administration has low bioavailability and it has large differences in individual absorption;animals can be found in obvious pain,great disturbance in subcutaneous injection.However,pouring agents can overcome the disadvantages of oral and injection of ivermectin administration.With the development of science and technology,the nanotechnology has been used in medicine widely.Nano-scale drug possesses the high dissolution rate and high dissolution saturation,which is very suitable for the application of ivermectin.In this study,beagle dogs and other dogs with demodex mites or roundworm infections in clinal trials were used as the experimental model.After the nanometer ivermectin pouring agent and ivermectin pouring agent treating,we compared the survival rate of infected animals,the number of mites under the microscope,the evaluation of clinical effects,and the reduction rate and negative rate of roundworm eggs,in order to indicate efficacy of ivermectin pouring agents.And we set kinds of concentration groups,including the high concentration group(1mg/kg),medium concentration group(0.5 mg/kg),low concentration group(0.2 mg/kg)to explore the effect of different nano-ivermectin pour agent concentration.The results showed:It was both 48 h of the zero to peak concentration in the ivermectin group and the nano-ivermectin group.The peak concentration of ivermectin pourer was 12.9 ng/m L,while the peak concentration of nanometer ivermectin pourer was 7.8 ng/m L.The MRT of the ivermectin pourer was 31.83 h,and the MRT of the nano-ivermectin pourer was 32.41 h;The AUC of the ivermectin pourer was 546.86 h?ng/m L,and the AUC of nano-Ivermectin pourer was 406.39 h.ng/m L.The pharmacokinetics of nano-ivermectin pourer and ivermectin pourer in dogs are basically similar,and the drug-time curve is basically parallel.Clinical treatment of dogs with natural infections of demodex canis and ascaris canis showed that the survival rate of experimental dogs in each group was 100%;the detection rate of worms on day 49 of nanometer ivermectin pourer treated was zero in the treatment of demodex canis and twice consecutive microscopy results were negative,which was earlier than the same dose of ivermectin pourer.In the treatment of ascaris canis infection,the worms reduction rate reached 100% on the 10 th day after the nano-ivermectin pouring agent 1 mg/kg,and the worms reduction rate reached 100% on the 15 th day of the 0.5mg/kg dose group,while the reduction rate of worms reached 100% on the 20 th day after the administration of the same dose(0.5 mg/kg)of ivermectin pouring agent.Compared with ivermectin pouring agents,the same amount of nano-ivermectin pouring agents can effectively shorten the treatment time;the efficacy of nano-ivermectin pouring agents increases with the increase of the dosage.The results show that the pharmacokinetic parameters of nano-ivermectin pouring agent are not superior to ordinary one,however,the effect is better under the premise of the same concentration in clinical practice.