Pharmacokinetics And Pharmacodynamics Of ECOHEART Chewables In Dogs

As an antiparasitic drug that belongs to the family of marocyclic lactone, Ivermectin (IVM) was widely used in the world. Heartworms can be prevented by Ivermectin under low dose while nematodes and arthopods can be killed under higher dose. Pyrantel has a good effect to many kinds of gastrointestinal nematodes. The pharmacokinetics of IVM in ECOHEART Chewables and its pharmacodynamics were investigated in Beagle dogs.Twelve healthy one-year-old Beagle dogs were used in pharmacokinetics study and were randomly divided into two groups. The dose of one group of dogs were10μg/kg b.w. through oral administration of ECOHEART Chewables and the other group were100μg/kg b.w. through subcutaneous administration of Yike MinDing solution. Blood samples were obtained at different time intervals respectively after administration. The concentration of IVM in dogs’plasma was determined by reverse high performance liquid chromatography (HPLC) with fluorescence detection. And all the plasma concentration-time datas were analyzed by3p97software.The working conditions of RP-HPLC were as follows:the stationary phase chromatographic column:ODS-2Hypesil C18(250mm×4.6mm,5μm), mobile phase: methanol:acetonitrile:0.2%acetic acid=55:43:2(v/v/v), flow rate:1mL/min, injection volume:100μL, column temperature:35℃, excitation wavelength:365nm, emission wavelength:475nm. Under these chromatographic conditions, the concentration of IVM in dogs’plasma showed a good liner relation(R2=0.9998) within the range of0.25～120ng/mL. The average recoveries were83.01%～91.75%. The within-day and between-day coefficients of variation were3.75%～6.45%and3.26%～8.86%respectively. The limit of detection was0.05ng/mL, and limit of quantification was0.25ng/mL.The plasma concentration-time data of Yike MinDing solution fitted to a one-compartment open model after single subcutaneous administration in dogs. The main pharmacokinetic parameters were as follows:ti/2(ka)(0.44±0.23) d, t1/2(ke)(3.21±0.74) d, t(peak)(1.47±0.43) d, C(max)(12.76±2.34) ng/mL, AUC (79.52±14.14)(ng/mL)·d, CL/f(s)(3.21±0.74) μg/kg/d/(ng/mL). The plasma concentration-time data of ECOHEART Chewables fitted to a two-compartment open model after single oral administration in dogs. The main pharmacokinetic parameters were as follows:t1/2(ka)(0.06±0.01) d, t1/2a (0.08±0.01) d, t1/2β (2.45±0.20) d, t(peak)(0.13±0.01) d, C(max)(4.25±0.35) ng/mL, AUC (9.35±1.18)(ng/mL)·d, CL(s)(1.09±0.14) μg/kg/d/(ng/mL), F117.58%.The above pharmacokinetic results showed that ECOHEART Chewables absorbed completely, distributed widely, eliminated slowly in the body and had a high relative bioavailability after oral administration in dogs.To confirm the helminthicide effect of ECOHEART Chewables, The pharmacodynamic contrast trial was investigated. Sixty vermiculous dogs were randomly divided into two groups. The body conditions of the tested dogs and types of infected worm eggs were similar. A single dose of one group of dogs were6μg/kg through oral administration of ECOHEART Chewables, and the other group of dogs were also given orally under the directions of Drontal(?) Plus Flavor by a single dose. The test period was15d. The mental state, eating desire, activity of dogs were observated twice a day within5days after administration, and the collected polypide and nodal plate must be identified. The fresh feces of dogs were collected on5,10,15days after administration. The saturated saline floatation method was used to checked if there were worm eggs and then the eggs types were identified, the eggs per gram feces and the reduction rate of eggs of worms in dogs were calculated with McMaster’s method. The results showed that the negative rates on the egg of ECOHEART Chewables to Toxocara, Toxascaris leonina and Ancylostoma caninumwere all up to100%, while the control drug was only76.5%,75.0%and87.5%separately. The symptoms of worm infection in dogs disappeared at the end of the trial. All of the results showed that both ECOHEART Chewables and Drontal(?) Plus Flavor had good therapeutical effect to dogs’worm infection, but the effect of ECOHEART Chewables was better.