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Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole
Savlík M, Fimanová K, Szotáková B, Lamka J, Skálová L
Jazyk angličtina Země Velká Británie
NLK
ScienceDirect (archiv)
od 1993-01-01 do 2009-12-31
- MeSH
- alkoholoxidoreduktasy metabolismus MeSH
- anthelmintika farmakologie MeSH
- fenbendazol farmakologie MeSH
- financování organizované MeSH
- glukuronosyltransferasa metabolismus MeSH
- izoenzymy MeSH
- jaterní mikrozomy enzymologie metabolismus účinky léků MeSH
- mebendazol analogy a deriváty farmakologie MeSH
- nemoci prasat enzymologie farmakoterapie parazitologie MeSH
- parazitární nemoci střev enzymologie farmakoterapie veterinární MeSH
- prasata MeSH
- steroidhydroxylasy metabolismus MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- tenké střevo enzymologie metabolismus účinky léků MeSH
- western blotting veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.
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- $a Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. savlik@faf.cuni.cz
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- $a Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.
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