Pharmacokinetic Interaction Of Ivermectin And Triclabendazole Following Co-administration To Helminths Infected Sheep

The pharmacokinetic properties of Ivermectin (IVM) and Triclabendazole (TCBZ) were evaluated in this study following administered separately and co-administered to helminths infected sheep.15Ordos merino sheep naturally infected with gastrointestinal parasites were received by IVM subcutaneously alone, given by TCBZ alone and combined administration of IVM and TCBZ, respectively. Heparinized blood samples were collected between0.75and336hours after treatment and immediately centrifuged to obtain the plasma, which were kept in-39℃till the time of analysis.The reversed-phase high-performance liquid chromatography (HPLC) with fluorescence detection method was developed for determining IVM concentration in plasma, and the Abamectin was used as an internal standard. Methanol was used to deposit proteins in plasma. The residue was centrifuged and then cleaned up by ODS C18SPE column. The eluate was evaporated, derived and dissolved with methanol before detected by HPLC.The mobile phase was organic solvent (methanol-acetonitrile)-water (95:5), and the flow-rate was1.0mL·min-1. The injection volume was20μL.The detector was fixed at an excitation wavelength of366nm and an emission wavelength of465nm at room temperature. In the chromatographic conditions above, IVM and AVM were well separated with retention time of8.37min,6.16min, respectively.HPLC method was developed for determination of TCBZ metabolites plasma by using Mebendazole as an internal standard. Methanol was used as precipitant to deposit proteins in plasma. The samples were analyzed by HPLC to determine the concentrations of TCBZSO and TCBZSO2after centrifuged, evaporated and dissolved with mobile phase. The mobile phase was a mixture of acetonitrile-ammonium acetate (0.025M, pH6.6) in a linear gradient fashion changing from52:48to60:40for5min, then70:30linearly lasts for8min, and the last proportion was52:48being continued for7min.The flow-rate was1.0mL/min at room temperature. The injection volume was50μL.At the chromatographic conditions above, TCBZ, TCBZSO, TCBZSO2and MBZ were well separated, with retention time of10.044min,5.535min,4.708min and3.420min.The concentrations of IVM, TCBZ, TCBZSO and TCBZSO2after administration were measured and pharmacokinetic characteristics were calculated by Phoenix WinNonlin (version6.2) using non-compartmental analysis (NCA) module. The pharmacokinetic properties of IVM and TCBZ were evaluated following either separately or co-administrated.The results showed that the Cmax and AUC of IVM after co-administration with TCBZ was significantly lower than the treatment with IVM alone. The Vd, T1/2ke and CLb were significantly higher than the treatment with IVM alone. The Vd, MRT and Tmax of TCBZSO were significantly higher after co-administration. The T1/2ke of TCBZSO was higher after co-administration. Consequently, there were some pharmacokinetic interactions when IVM and TCBZ combined in helminthes infected sheep, we should pay attention to this in clinical practices accordingly.