ATCvet code: QP52AF02.
Fixed combination of two anthelmintics: a tetrahydro-pyrimidine derivative, pyrantel (as the embonate) and a pro-benzimidazole, febantel.
Pharmacodynamics
In this fixed combination product, the pyrantel and febantel act synergistically against nematodes (ascarids, hookworms and whipworms) of dogs. In particular, the spectrum of activity covers Toxocara canis, Ancyclostoma caninum and Trichuris vulpis. Published data are also available to confirm that Toxascaris leonina and Uncinaria stenocephala are also susceptible to this particular combination of actives.
Febantel, N-{2-[2,3-bis,(methoxycarbonyl)-guanidino]-5-(phenylthio) phenyl}-2- methoxyacetamide, is a pro-benzimidazole. Within the mammalian system febantel undergoes ring closure forming fenbendazole and oxfendazole. It is these chemical entities which exert the anthelmintic effect by inhibition of tubulin polymerization. Formation of microtubules is thereby prevented, resulting in disruption to structures vital to the normal functioning of the helminth. Glucose uptake, in particular, is affected, leading to depletion in cell ATP. The parasite dies upon exhaustion of its energy reserves, which occurs 2-3 days later.
Pyrantel, (E)-1,4,5,6-Tetrahydro-1-methyl-2-[2-(2-thienyl) vinyl] pyrimidine pamoate belongs to the tetrahydropyrimidine type. Its mode of action is to stimulate nicotinic cholinergic receptors inducing spastic paralysis and thereby allowing removal from the gastro-intestinal (GI) system by paralysis.
Pharmacokinetics
Literature reports indicate after oral application of the recommended dose of 1 ml/kg bodyweight (corresponding to 14.4mg/kg pyrantel embonate and 15 mg/kg febantel) maximum serum concentrations for febantel were found between 1 and 6 hours with with a Cmax of 0.019 mg/l two hours after dosing. As febantel as a pro-drug is metabolised to fenbendazole which is further converted to oxfendazole, also these metabolites were measured. Cmax of febendazole was 0.130 mg/l after 3 hours and Cmax of oxfendazole was 0.157 mg/l at about 5 hours after application.
The Cmax of pyrantel (measured as pyrantel base) was 0.084 mg/l 2.5 hours after application.