Document Detail

Methimazole-mediated modulation of netobimin biotransformation in sheep: a pharmacokinetic assessment.
MedLine Citation:
PMID:  1433490     Owner:  NLM     Status:  MEDLINE    
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 (ABZSO2). 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 i.m.). ABZSO AUCs were significantly higher (P less than 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 +/- 0.68 h (control treatment), 18.85 +/- 2.35 h (NTB + MTZ oral) and 17.02 +/- 0.90 h (NTB + MTZ i.m.). There were no major changes in the overall pharmacokinetics of ABZSO2 for the concomitant MTZ treatments. However, delayed appearance of this metabolite in the plasma resulted in longer ABZSO2 lag times and a delayed Tmax for treatments with MTZ.(ABSTRACT TRUNCATED AT 250 WORDS)
C E Lanusse; L Gascon; R K Prichard
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of veterinary pharmacology and therapeutics     Volume:  15     ISSN:  0140-7783     ISO Abbreviation:  J. Vet. Pharmacol. Ther.     Publication Date:  1992 Sep 
Date Detail:
Created Date:  1992-11-27     Completed Date:  1992-11-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7910920     Medline TA:  J Vet Pharmacol Ther     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  267-74     Citation Subset:  IM    
Institute of Parasitology of McGill University, Macdonald College, Ste-Anne de Bellevue, Québec, Canada.
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MeSH Terms
Administration, Oral
Albendazole / analogs & derivatives,  blood
Anthelmintics / administration & dosage,  blood,  pharmacokinetics*,  pharmacology*
Biotransformation / drug effects
Chromatography, High Pressure Liquid
Guanidines / pharmacokinetics*
Injections, Intramuscular / veterinary
Methimazole / administration & dosage,  blood,  pharmacology*
Sheep / metabolism*
Reg. No./Substance:
0/Anthelmintics; 0/Guanidines; 54029-12-8/albendazole sulfoxide; 54965-21-8/Albendazole; 60-56-0/Methimazole; 76567-28-7/albendazole sulfone; 88255-01-0/netobimin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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