title: Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole.
abstract: 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.
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. savlik@faf.cuni.cz
authors.forename: M
authors.initials: M
authors.lastname: Savlík
authors.forename: K
authors.initials: K
authors.lastname: Fimanová
authors.forename: B
authors.initials: B
authors.lastname: Szotáková
authors.forename: J
authors.initials: J
authors.lastname: Lamka
authors.forename: L
authors.initials: L
authors.lastname: Skálová
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D015153:Blotting, Western / Q000662:veterinary; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005273:Fenbendazole / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D007411:Intestinal Diseases, Parasitic / Q000188:drug therapy / Q000201:enzymology* / Q000662:veterinary*; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes; D008297:Male; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000469:parasitology*
chemical_list: D000871:Anthelmintics; D007527:Isoenzymes; D005273:Fenbendazole; D008463:Mebendazole; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; D013250:Steroid Hydroxylases; D014453:Glucuronosyltransferase; C018945:flubendazole