Fenbendazole and thiabendazole in cattle: partition of gastrointestinal absorption and pharmacokinetic behaviour.
Fenbendazole (FBZ) and thiabendazole (TBZ) were administered intraruminally with a single dose of an indigestible marker, chromium ethylenediaminetetra-acetate (Cr-EDTA), to cattle fitted with gastrointestinal cannulae. The amounts of anthelmintic leaving the rumen, abomasum and terminal ileum in digesta were derived by compartmental analysis of Cr-EDTA concentrations and integration of benzimidazole concentrations. TBZ was absorbed much more rapidly from the rumen than FBZ and only about 12% of the dose left the rumen in digesta compared with 30% of the FBZ. Approximately 10% and 8% of the TBZ dose appeared at the pylorus and terminal ileum, respectively. Of the above amounts, 9% in the abomasum and practically 100% in the ileum was present as 5-OH-TBZ, indicating that metabolites of absorbed TBZ were recycled to the gastrointestinal tract. Twenty-eight percent and 52% of the FBZ appeared at the pylorus and terminal ileum, respectively, indicating a substantial recycling of absorbed drug to the small intestine. It is suggested that biliary secretion of both TBZ and FBZ and their metabolites may contribute to this recycling. Maximal concentrations of TBZ occurred in plasma in 4 h compared with about 24 h for FBZ. TBZ and metabolites were excreted in urine much more rapidly than were FBZ and metabolites. In plasma and in each of the gastrointestinal compartments, FBZ persisted much longer than did TBZ. It was concluded that slower absorption and excretion and more extensive recycling to the gastrointestinal tract of FBZ, than of TBZ, contribute markedly to its greater potency against helminths.
D000018:Abomasum / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism*; D002417:Cattle / Q000378:metabolism*; D005273:Fenbendazole / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism; D006900:Hydroxylation; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D012417:Rumen / Q000378:metabolism; D013827:Thiabendazole / Q000378:metabolism*; D013997:Time Factors
D001562:Benzimidazoles; D005965:Glucuronates; D005273:Fenbendazole; D013827:Thiabendazole