Effects of methimazole on the kinetics of netobimin metabolites in cattle

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Abstract
1. The effects of methimazole (MTZ) on the pharmacokinetic behaviour of netobimin (NTB) and its albendazole (ABZ) metabolites were studied in calves. NTB trisamine salt solution was given by subcutaneous (12.5 mg/kg) and oral (20 mg/kg) routes, either alone or co-administered with MTZ (1.5 mg/kg, intramuscularly). 2. NTB parent drug was detected only after s.c. treatments, showing rapid absorption, early Cmax and fast disposition. ABZ was not found in plasma at any time after either s.c. or oral treatments. 3. Concomitant treatment with MTZ significantly increased the albendazole sulphoxide (ABZSO) elimination half-life (t1/2β) (321%) and mean residence time (MRT) (170%) from the values obtained after s.c. treatment with NTB alone. 4. Oral treatment resulted in an ABZSO pharmacokinetic profile with an AUC 27% higher, a significantly longer t1/2β (151%) and MRT (124%) in the presence of MTZ. 5. We conclude that when co-administered with NTB in cattle, MTZ induces significant changes in the disposition kinetics of the anthelmintically active ABZSO metabolite.