Abstract: 【Objective】 The objective of this study is to illustrate the pharmacokinetic characteristics and interactions of ivermectin and triclabendazole in helminth infected sheep following co-administration. 【Method】 A total of 15 Ordos merino sheep in lactation period of 4 years old, average body weight of (39.3±3.2) kg, naturally infected with gastrointestinal helminth (EPG≥1500) were selected by using McMaster’s method. The testing sheep were randomly divided into 3 treatment groups of 5 sheep in each group. The sheep in groupⅠ were subcutaneously injected with IVM alone (0.2 mg•kg-1), that in groupⅡ were orally administered with TCBZ alone (15 mg•kg-1), and that in groupⅢ were combined administrated with TCBZ (15 mg•kg-1 po.) and IVM (0.2 mg•kg-1, sc.). 5 mL of blood samples were collected from the jugular vein from 0.75, 2, 4, 8, 16, 24, 36, 48, 72, 120, 192 and 336 h after administration, and the concentrations of IVM, TCBZ and TCBZSO in each sample were detected by high-performance liquid chromatography (HPLC) with fluorescence detection and UV detection, respectively. Chromatographic conditions: a reversed-phase C18 column, InertsilODS-SP (5 µm, 4.6×150 mm, I.D.); mobile phase of V (methanol and acetonitrile)﹕V (water) =95﹕5; excitation wavelength of 364 nm, emission wavelength is 470 nm; the flow rate was 1.0 mL•min-1; column temperature was at room temperature; the injection volume was 20 µL. The pharmacokinetic characteristics were calculated by Phoenix WinNonlin using non-compartmental analysis (NCA) model. 【Result】The results showed that the chromatographic peaks of IVM and internal standard AVM were well separated with retention time of 8.73 min and 6.16 min, which were not influenced by the other interfering peaks of plasma. The retention time of TCBZ, TCBZSO and internal standard of mebendazole were 10.04 min, 5.53 min and 3.42 min, respectively, and well seperated with no interfering peaks. Therefore, the methods established in this study are feasible to detect different targets in testing samples. For IVM, peak plasma concentration (Cmax) and area under the concentration time curve (AUC) were decreased significantly, however, the apparent volume of distribution (Vd), elimination half-life (T1/2ke) and body clearance (CLb) were increased significantly following combined administration of IVM and TCBZ. For TCBZSO, Vd, mean residence time (MRT) and Tmax were significantly increased, however, T1/2ke was significantly decreased in co-administration group. 【Conclusion】In conclusion, the ivermectin and triclabendazole was pharmacokinetically interacted each other following combined use in helminth infected sheep and sufficient attention should be paid to co-administration of them in clinical practices. In order to ensure the full play of the original drug efficacy and synergistic action, the blind compatibility and combination of drugs only based on the in vitro pharmacodynamic synergism should be avoided.

Key words: ivermectin , triclabendazole , co-administration , pharmacokinetic interaction