Studies On An Injection Of Eprinomectin

Avermectins are widely used as an antiparasitic against nematodes and arthropods. Among these drugs, Eprinomectin exhibits higher potency and lower residue. Eprinomectin is the exclusive avermectin that can be applied in beef and dairy cattle with a zero slaughter withdrawal period and zero milk discard. Until now, the licensed pour-on formulation is'the only available product of eprinomectin. To reduce the dose of administration and improve the bioavailability, a serials of studies on an injection of eprinomectin were conducted.A sustained-release injection of eprinomectin as one per cent was developed. A method of determination of eprinomectin in the injection by high performance liquid chromatograph (HPLC) was developed. Stability of the injection in two years showed that the injection was stable, the useful life is 23.97 months. Acute toxicity in rats by oral administration exhibited that the injection has a low toxicity.An internal standard method was developed for determination of eprinomectin in plasma and milk by high-performance liquid chromatography with fluorescent detection using doramectin as an internal standard. Methanol and acetonitrile was applied in extracting eprinomectin and depositing proteins in plasma and milk, respectively. The extract was purified by ODS C18 SPE column. The eluate was dried. The residue was derived by methylimidazole and triflaoreacetic anhydride under heating condition, with addition of glacial acetic acid. Then the derivatives of eprinomectin and dormectin were detected by HPLC system. The mobile phase of A solution (methonal -acetonitrile = 2:l,v/v)/water (98:2) at a flow rate of 1.0ml min-1. The column temperature was room temperature. The injection volume was 100 1. The detector was fixed at an excitation wavelength of 366nm and an emission wavelength of 465nm. The method employs 2ml plasma samples and gives a good linear (r2=0.999) and high recovery (94.90-111.65%) over the concentration from 1 to 80ng ml-1. This method permits the determination of eprinomectin in plasma at level as low as 0.08 ng ml-1. The method gives a good linear (r2=0.997) and high recovery (83.4-105.65%) over the concentration in milk from 1 to 40 ng ml-1. The determination limit in milk is 0.1 ng ml-1.Pharmacokinetics of eprinomectin in plasma and milk following subcutaneous administration to lactating dairy cattle was conducted. Eprinomectin attained peak in plasma (Cmax, 44.0ng/ml) 39 hours (Tmax) after administration. The half-life of absorption and elimination was 11.9h and 164h, respectively. The area under the curve (AUC) was 7354 ng-h/ml. The mean residue time (MRT) was 221h. These results demonstrated the bioavailability of eprinomectin following subcutaneous injection was higher than topical administration. Eprinomectin reached the peak in milk (Cmax, 6.39ng/ml) 49.8h (Tmax) after injection. The detected peak of eprinomectin in milk was 9.00ng/ml. The residue of eprinomectin in milk doesn't exceed the maximum residue limit of eprinomectin in milk (20ng/ml) established by FAO. The AUC in milk was 1194 ng.h/ml. The MRT was 765h. The milk to plasma ratio was 0.16.Eprinomectin has an ultimate efficacy against ear mite in rabbit, mites in sheep, nematodes in sheep and beef cattle, louse in beef cattle following subcutaneous administration at a dose of 0.2mg/kg. The duration period of eprinomectin against ear mite in rabbit is 35 days. The duration period of eprinomectin against mites in sheep and nematodes in sheep and cattle is 42 days.