Preliminary Preclinical Studies On The Transdermal Penetration Of Fluazuron

Fluazuron,which has been used for controling Boophilus microplus in a foreigncountry, is a benzoyl urea chitin synthesis inhibitors.In order to evaluate the safety; observethe effect for controling Rhipicephalus sanguineus and pharmacokinetic characteristics offluazuron in dogs,our group carried out a preliminary study on the acute toxicity,pharmacodynamic and pharmacokinetic.Acute toxicity test of fluazuron active ingredient and transdermal agent wereconducted with Maximum dosage experiment method and Karber method following oraland topical administration in mice.Toxi and side-effect of transdermal agent were observedin mice by topical administration.On the basis of the acute toxicity test, Canine which weretreated with different doses of transdermal agent were artificially infected byRhipicephalus sanguineus adults, and then the blood female Rhipicephalussanguineus,collected by the canine, were hatched under laboratory conditions, and adultoviposition and larval hatching were recorded to evaluate the effect of transdermal agent tothe killing effect of adults control effect.2mg·kg-1dose percutaneous fluazurontransdermal agent was given to six selected healthy dogs, and canine peripheral blood werecollected at different time points, the serum was then separated.This article establishedHPLC method for the determination of plasma concentration,and the pharmacokineticparameters were calculated by Phoenix WinNonlin6.3software using non-compartmentalmodel.The results showed that mice oral fluazuron LD50value of＞16000mg·kg-1, mouseoral formulation LD50equal to5859.4mg·kg-1, and the preparation of transdermal drugdelivery The LD50is greater than10000mg·kg-1. Fluazuron Rhipicephalus sanguineuslarvae LD50, LD950.7762mg·kg-1and3.3237mg·kg-1, respectively; have the effect ofdifferent doses of transdermal agent of adult breeding. The pharmacokinetic studiesshowed that the established method of measuring fluoride in serum the ticks ureaconcentration in the10to200ng·mL-1within the scope of the peak area showed a goodlinear relationship, the linear regression equation was A=0.0348C+0.0153, the lowestdetection limit of10ug·L-1, the lower limit of quantification of20ug·L-1. The recovery inthe range of96.17%to118.33%, day relative standard deviation (RSD)≤3.83%, the thedaytime relative standard deviation (RSD)≤6.35%. Non-compartmental modeling fluorineticks urea preparations in dogs pharmacokinetics, and its main parameters Tmax=39h,Cmax=156.8942ng·ml-1, T1/2=32.7206d, CL=0.1183L·kg-1·h-1, AUX=135619.7ng·h·mL-1. Using SPSS software to analyze the plasma concentration of the different dogseach time point, six dogs between individuals, no significant differences (P>0.05)wereobsereved in the female group and male group.Conclusion:1, raw materials under therapeutic dose and preparations of fluazuron inmice is considered as low acute toxicity;2, Rhipicephalus sanguineus has better controleffect;3, this paper establishes a high-performance liquid chromatographic method whichis suitable for the determination of canine serum fluazuron content in the pharmacokineticstudy.