Pharmacokinetic Behavior Of Ivermectin And Albendazole Following Co-administration To Helminth Infected Sheep

To illustrate the combined use of ivermectin and albendazole pharmacokinetic characteristics in helminth infected sheep, the pharmacokinetic properties of ivermectin (IVM) and Albendazole (ABZ) were evaluated in this study following either separately or co administered to helminth infected sheep.15 Ordos merino sheep naturally infected with gastrointestinal parasites were allocated into 3 treatment groups of 5 sheep in each group: (Ⅰ) single oral administration of ABZ (15 mg/kg), (Ⅱ) IVM subcutaneous alone (0.2 mg/kg), (Ⅲ) combined administration of ABZ (15 mg/kg,or) and IVM (0.2 mg/kg, sc). Blood samples were collected from the jugular vein from 0.75 to 720 hours after administration. The blood samples obtained were immediately centrifuged to obtain the plasma,which was stored at -38℃until the day of analysis.An internal standard method was developed for determination of IVM plasma by high-performance liquid chromatography with fluorescent detection using abamectin as an internal standard. Methanol was applied in extracting IVM and depositing proteins in plasma. The extract was purified by ODS C18 SPE column. The eluate was dried. The residue was derived by methylimidazole and triflaoreacetic anhydride.Then the derivatives of IVM and ABM were deteeted by HPLC system.The mobile Phase of A solution(methonal-etonitrile=1:1,v/v)/water(100:5) at a flow rate of 1.0 ml/min.The column temperature was room temperature.The injection volume was 50μL. The detector was fixed at an excitation wavelength of 366nm and an emission wavelength of 465nm. Under the described chromatographic conditions, Ivermectin and Avermectin were well resolved with no interference from endogenous compounds and with retention times of 9.16min, 14.61 min, respectively. An internal standard method was developed for determination of ABZ metabolites plasma by high-performance liquid chromatography using menbendazole as an internal standard. Acetonitrile was applied in extracting ABZ metabolites. After a liquid-liquid extraction, the samples were analysed by HPLC to determine the concentrations of ABZSO and ABZSO2. The mobile phase was a mixture of acetonitrile–water to which glacial acetic acid was added (0.5%, v/v) in a linear gradient fashion changing from 20:80 (acetonitrile–water) to 30:70 for 8 min then 30:70 to 55:45 for 22 min, and the last ratio from 55:45 to 20:80 being maintained for 7 min.The flow rate was 1 ml/min. The column temperature was room temperature. The injection volume was 20μL. Under the described chromatographic conditions, ABSSO, ABZSO2 and MBZ were well resolved, with no interference from endogenous compounds and with retention times of 8.75, 11.97 and 18.56 min, respectively.The pharmacokinetics of IVM and ABZ metabolites were conducted in sheep With naturally infected helminthes.The results showed that the IVM Cmax and MRT obtained after its co-administration with ABZ was significantly lower than the treatment with IVM alone. Although, the AUC values for IVM obtained after its co-administration with ABZ were lower than the treatment with IVM alone, the parameter did not reach statistical significance. When combined used of ABZ and IVM, the lag times of ABZ metabolites were significantly prolonged. Although the other pharmacokinetic parameters were not significantly difference, however, the AUC of ABZSO and ABZSO2 were shown a downward trend while Vd of them was shown increasing trend in concurrent administration of IVM group. Therefore, there were some pharmacokinetic interactions when combined use of Ivermectin and albendazole in helminth infected sheep and sufficient attention should be paid on concurrent administration of them in clinical practices.