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Methimazole‐mediated modulation of netobimin biotransformation in sheep: a pharmacokinetic assessment
Author(s) -
LANUSSE C. E.,
GASCON L.,
PRICHARD R. K.
Publication year - 1992
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1992.tb01016.x
Subject(s) - pharmacokinetics , metabolite , chemistry , oral administration , pharmacology , medicine , biochemistry
The effects of modulation of liver microsomal sulphoxidation on the disposition kinetics of netobimin (NTB) metabolites were investigated in sheep. A zwitterion suspension of NTB was given orally at 7.5 mg/kg to sheep either alone (control treatment) or co‐administered with methimazole (MTZ) orally (NTB + MTZ oral treatment) or intra‐muscularly (NTB + MTZ i.m.) at 3 mg/kg. Blood samples were taken serially over a 72 h period and plasma was analysed by HPLC for NTB and its major metabolites, i.e. albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO 2 ). Only trace amounts of NTB parent drug and ABZ were detected in the earliest samples after either treatment. There were significant modifications to the disposition kinetics of ABZSO in the presence of MTZ. ABZSO elimination half‐life increased from 7.27 h (control treatment) to 14.57 h (NTB + MTZ oral) and to 11.39 h (NTB + MTZ im.). ABZSO AUCs were significantly higher (P < 0.05) for the NTB + MTZ oral treatment (+55%) and for the NTB + MTZ i.m. treatment (+61%), compared with the NTB alone treatment. The mean residence times for ABZSO were 12.66 5 0.68 h (control treatment), 18.85 ± 2.35 h (NTB + MTZ oral) and 17.02 ± 0.90 h (NTB + MTZ im.). There were no major changes in the overall pharmacokinetics of ABZSO 2 for the concomitant MTZ treatments. However, delayed appearance of this metabolite in the plasma resulted in longer ABZSO 2 lag times and a delayed T max for treatments with MTZ. We have demonstrated that co‐administration of MTZ, both orally and intra‐muscularly, results in an altered pharmacokinetic pattern for the metabolites of NTB. The changed pharmacokinetic profile of the anthelmintically‐active ABZSO metabolite may result in enhanced efficacy.