Preparation And Preliminary Study On Pharmacokinetics In Dogs Of Flumethrin Pour-on Preparation

Flumethrin (flumethrin,flu) is a kind of α-cyano Ⅱ pyrethroid pesticides.It has high performance and low toxicity.it can inhibit spawning and hatching for prevention and treatment of animal exoparasite.It’s one of the most promising antiparasitic medicine currently.The preparation and pharmacokinetics in dogs of flumethrin pour-on preparation was studied in this paper.1Formulation optimized experiment of flumethrin pour-on preparationThis experiment was conducted to optimize the formulation of flumethrin pour-on preparation. The concentration of flumethrin was determined by HPLC.We prepared nine different kinds of pour-on preparations which had different proportions of acetic ether, azone, propylene glycol and alcohol.These formulations were optimized by the drug permeate rate in vitro.Then repetitive trial was done with the optimized formulation.The results showed that the condition of HPLC was as follows:C18column (150mm×4.8mm,5μm),mobile phase was a mixture of acetonitrile and water(87:13).The flow rate was0.8mL/min and the detection wavelength was292nm.Injection volumn was20μL and column temperature was30℃.Retention time of flumethrin was7.5～7.6min.The optimized formulation was the third formulation which permeate rate was300.2μg·cm-2·h-1.The Js of repetitive trial approached to formulations optimized result.The optimized formulation possed a high drug permeate rate in vitro which exhibit stable and reliable.2Determination the content and stability of flumethrin pour-on preparationA HPLC method was established for determination of flumethrin pour-on preparation concention.The stability was estimated by illumination-test,accelerating-test and term-test.The condition of HPLC was as follows:C18column (150mm×4.8mm,5μm),the mobile phase was acetonitrile:water (87:13),the flow rate was0.8mL/min, the detection wavelength was292nm,injection volumn was20μL and column temperature was30℃.The content of flumethrin pour-on preparation was98.2%of labelled amount.The content decreased to86.87%and the color changed from yellow to yellowish and permeat rate decreased from299.34to225.83μg·cm-2·h-1after illumination of4500±5001x for10days.The content decreased less than5%,the color and permeat rate were not changed after6months accelerating-test and9months long term-test.The results showed that the method was rapid,simple and accurate for the content determination of flumethrin.The preparation was unstabile to light.So it should be packed in brown bottle and saved in darkness.There were no conspicuous changes after6months accelerating-test and9months long term-test which showed it accorded with the regulation of vaterinary drug quality criterion.3Skin irritation and sensitization experiments of flumethrin pour-on preparationThis experiment was conducted to investigate whether flumethrin pour-on preparation had the side effect of irritation and sensitization to skin.The irritation of flumethrin pour-on preparation was observed in integrated and impaired skin by means of autogenous contrast in rabbit.The sensitization of flumethrin pour-on preparation was observed in guineapig by means of Buehler experiment.The results showed that there was no abnormal reaction in skin of rabbit and the ratio of sensitization of flumethrin pour-on preparation to guineapig was zero.We concluded that flumethrin pour-on preparation had no side effect of irritation and sensitization to skin and was safe for experimental animals.4Preliminary studies on pharmacokinetics of flumethrin in dogsPharmacokinetics of flumethrin pour-on preparation(1%) was studied in healthy dogs.Flumethrin pour-on preparation were dermal administrated in a dose of2mg/kg-bw in6healthy dogs and the plasma concentration of flumethrin was detected by RP-HPLC.The concentration-time data were analyzed with3P97computer program.The results suggested that the pharmacokinetics characteristics was fit to two-compartment model with first order absorption rate.The main pharmacokinetics parameters were as follows:T1/2α was3.622±1.079h,T1/2β was22.654±0.417h,T1/2Ka was1.684±0.240h,AUC was47.385±1.709μg·mL-1·h,Tpeak was4.165±0.187h,Cmax was1.902±0.064μg/mL,Lag-time was0.489±0.002h.We concluded that flumethrin both been absorbed and eliminated slowly and had a long persistence time.