| Eprinomectin as a munber of avermectins, is the only broad-spectrum antiparasitic drugs licensed for treatment of parasitic infections in lactating cows without withdrawtime, which is very suited to use for the yak pasture in tableland. However, there are no reports on the use of commercial eprinomectin pour-on formulations for yak. To provide scientific basis for the application of eprinomectin pour-on formulation in yak and for ensuring food safety, this thesis focus on the pharmacokinetics, depletion and Pharmacodynamics of eprinomectin following topical administration in yaks.A HPLC-FLD method was developed for determination of residues of eprinomectin in plasma and milk of yaks. The limit of detection (LOD) was 0.01 ng-ml-1, and the limit of quantification (LOQ) was 0.5 ng-ml-1 in yak plasma; 0.08 ng-ml"1 and 0.2 ng-ml-1 in yak milk. The extraction recovery of eprinomectin was 98.4%-101.5% from plasma and 96.5%～102.4% from milk. The intra-and interassay coefficients of variation were 4.2%～6.7% and 2.3%～5.7% for plasma,2.7%～3.5% and 0.5%～8.1%for milk。Pharmacokinetics of eprinomectin in lactating yaks with the bioequivalence between generic drug (test group) and control grouop were evaluated. The results show that after topical administration of eprinomectin at a dose of 0.5 mg-kg-1, test group and the control group toke 1.67±0.2 d andl.83±0.61 d (Tmax) to reached Cmax 7.88±2.68 and 5.94±2.80 ng·ml-1, absorption half-life were 3.54±1.26 and 4.95±2.36 d, and the elimination half-life were 10.80±1.62 and 4.88±1.00 d respectively, AUC were 7.99±27.18 and 62.25±14.24 ng·d·ml-1, MRT was15.12±2.77 and 11.38±3.25 d respectively, the test group and a control formulation of eprinomectin is bioequivalence.The elimination of eprinomectin after topical administration in yak milk were carry on. In the test and control group of eprinomectin, it toke 2.40±0.89 and 3.00±2.53 d to reached the Cmax at 4.52±2.58 and 1.97±0.94 ng·ml-1, AUC were 32.96±19.66 and 14.71±6.26 ng·d·ml-1, MRT were 11.08±3.72 d and 9.75±2.86 d, the milk to plamsa ratio was 0.38±0.23 and 0.24±0.08 respectively。The detected peak of eprinomectin in milk was 8.46 ng·ml-1. The residue of eprinomectin in milk doesn’t exceed the MRL of eprinomectin in milk (20ng·ml-1) establihsed by FAO.To detect the tissue residue of eprinomectin, A HPLC-FLD method was developed. The limit of detection (LOD) was 0.01 ng·g-1, and the limit of quantification (LOQ) was 0.15 ng·g-1 in yak muscle; 0.10 ng·g-1 and 0.35 ng·g-1 in liver; 0.08 ng·ml-1 and 0.20 ng·g-1 in kidney; 0.10 ng·g-1 and 0.35 ng·g-1 in kidney. The extraction recovery of eprinomectin was 102.39%～108.93% from suscle,96.76%～97.78% from liver,91.60%～97.07% from kidney and 96.12%～97.42% from fat. The intra- and interassay coefficients of variation were 1.35%～5.82% and 4.09%～15.41% for muscle,2.22%～4.68% and 4.23%～15.07% for liver,1.26%～5.31% and 2.15%～3.19% for kidney,1.99%～4.78% and 2.04%～8.92% for fat.Then the back muscle, leg muscle, liver, kidney and fat samples were collected at planed time after topical administration of recommended dosage. It is spended 2d to reached the Cmax at a range of 15.00～1050.50 ng·g-1, and the AUC was 54.81～1506.76 ng·d·g-1, and the average residence time was in the range of 8.06～11.60 d, which was consistent with elimination half-life of 2.07～10.11 d. The raw data were analysed with WT1.4 program, the withdrawal period of yak muscle tissue and adipose tissue were zero, for liver was 8.94 d, while for kidney was 9.61 d. Results showed that the withdrawal time of eprinomectin in yak was at least 10 d.Finally, eprinomectin has an ultimate efficacy against Hypoderma spp., Linognathus vituli and gastrointestinal nematode in yak at a dose of 0.5 mg·kg-1 following topical administration. The duration period of Moxidectin against L.vituli and gastrointestinal nematode is at least 28d. |
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