The effects of fenbendazole, flubendazole and mebendazole on activities of hepatic cytochromes P450 in pig.

Article Details

Citation

Baliharova V, Velik J, Savlik M, Szotakova B, Lamka J, Tahotna L, Skalova L

The effects of fenbendazole, flubendazole and mebendazole on activities of hepatic cytochromes P450 in pig.

J Vet Pharmacol Ther. 2004 Apr;27(2):85-90. doi: 10.1111/j.1365-2885.2004.00557.x.

PubMed ID
15096105 [ View in PubMed
]
Abstract

Fenbendazole (FBZ), flubendazole (FLBZ) and mebendazole (MBZ) are benzimidazole anthelmintics widely used in veterinary medicine. The effects of these drugs on cytochromes P450 (CYP) were investigated in primary cultures of swine (Sus scrofa f. domestica) hepatocytes. After 48-h incubation of hepatocytes with benzimidazoles (0.1-2.5 microm), ethoxyresorufin O-deethylation (EROD), benzoxyresorufin O-dearylation (BROD), testosterone hydroxylase (6beta-TOH) and testosterone oxidase (17-TO) activities were measured and the CYP1A and 3A protein levels were determined by Western blotting. FBZ produced a significant, concentration-dependent increase of CYP1A activity (EROD) and protein level. No enhancement of CYP1A was observed after exposure to FLBZ and MBZ. All benzimidazoles tested did not cause any induction of CYP3A (BROD, 6beta-TOH, 17-TO activities and protein content). On the other hand, MBZ produced a significant, concentration-dependent decrease of CYP3A (BROD, 6beta-TOH and 17-TO) activities. Pharmacological and toxicological consequences of CYP1A induction and CYP3A inhibition should be taken into account in treatment of pigs with FBZ and MBZ.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
MebendazoleCytochrome P450 3A Subfamily (Protein Group)Protein groupHumans
Unknown
Substrate
Details
Drug Interactions
DrugsInteraction
Mebendazole
Phenytoin
The serum concentration of Mebendazole can be decreased when it is combined with Phenytoin.
Mebendazole
Fosphenytoin
The serum concentration of Mebendazole can be decreased when it is combined with Fosphenytoin.
Interactions
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