Anthelmintics. Benzimidazoles and related substances.
ATCvet code: QP52AC12
Flubendazole is a benzimidazole anthelmintic. It acts by binding to tubulin of the parasite, the dimeric subunit protein of the microtubules. It inhibits micro tubular assembly in absorptive cells: i.e. in intestinal cells of nematodes or the tegumental cells of cestodes. This is shown by disappearance of cytoplasmic microtubules, accumulation of secretory granules in the cytoplasm due to a block in their transport, leading to an impaired coating of the cellular membrane and a decreased digestion and absorption of nutrients. Irreversible lytic degeneration of the cells, due to the accumulation of secretory substances (hydrolytic and proteolytic enzymes) results in the death of the parasite. These changes are relatively fast and are primarily seen in those organelles directly involved in the secretory and absorptive functions of the cells. In contrast the changes are not seen in cells of the host. Another tubulin-related effect is the strong inhibition of egg hatch by inhibition of microtubule-depended processes in the developing worm egg (cell division).
Flubendazole is poorly soluble in aqueous systems, such as the gastrointestinal tract, which results in a low distribution rate and a low absorption. This is reflected by the high faecal excretion of unchanged parent drug. The small fraction absorbed is extensively metabolised by first-pass metabolism in the liver, involving carbamate hydrolysis and ketone reduction. The biotransformation products are conjugated to glucuronides or sulphate conjugates and excreted with the bile and the urine. The excretion with urine is relatively low and consists almost exclusively of metabolites with only small amounts of unchanged compound. In pigs and chickens, the half-life of flubendazole and its metabolites in plasma is 12 hours to 2 days.