Enhancement of the plasma concentration of albendazole sulphoxide in sheep following coadministration of parenteral netobimin and liver oxidase inhibitors

The effects of methimazole (MTZ), metyrapone (MTP) and quinine (QNE) on the pharmacokinetics and bioavailability of parenterally administered netobimin (NTB) and its major metabolites, albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2), were studied in sheep. NTB trisamine solution was first administered alone at 20 mg kg-1 by subcutaneous injection and then coadministered with either MTZ (1.5 mg kg-1 intramuscularly), MTP (20 mg kg-1 subcutaneously) or QNE (30 mg kg-1 intraruminally) in adult sheep. Blood samples were taken serially over a 120 hour period and plasma was analysed for NTB and its metabolites by high performance liquid chromatography. NTB parent drug showed a similar pharmacokinetic behaviour after all parenteral treatments. Both ABZSO AUCs (P less than 0.01) and Cmax (P less than 0.05) were significantly higher in the presence of MTZ and MTP than with the treatment with NTB alone. In the presence of each of the oxidation inhibitor compounds, the ratio of AUC ABZSO/ABZSO2 was significantly higher than with the NTB alone treatment. It has been demonstrated that the coadministration of substances which alter liver microsomal oxidation resulted in a modified pharmacokinetic pattern for the metabolites of NTB. Both NTB + MTZ and NTB + MTP treatments resulted in an improved pharmacokinetic profile for the anthelmintically active ABZSO metabolite.