Pharmacodynamic properties
In this fixed combination product pyrantel and febantel act against all relevant nematodes (ascarids, hookworms and whipworms) in dogs. In particular, the activity spectrum covers Toxocara canis, Toxascaris leonina, Uncinaria stenocephala, Ancylostoma caninum and Trichuris vulpis. This combination shows synergistic activity in the case of hookworms and febantel is effective against T. vulpis. The spectrum of activity of praziquantel covers all important cestode species in dogs, in particular all Taenia spp, Dipylidium caninum, Echinococcus granulosus and Echinococcus multilocularis. Praziquantel acts against adult and immature forms of these parasites.
Praziquantel is very rapidly absorbed and distributed throughout the parasite. Both in vitro and in vivo studies have shown that praziquantel causes severe damage to the parasite integument, resulting in contraction and paralysis. There is an almost instantaneous tetanic contraction of the parasite musculature and a rapid vacuolisation of the syncytial tegument. This rapid contraction has been explained by changes in divalent cation fluxes, especially calcium.
Pyrantel acts as a cholinergic agonist. Its mode of action is to stimulate nicotinic cholinergic receptors of the parasite, induce spastic paralysis and thereby allow removal from the gastrointestinal system by peristalsis.
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 polymerisation. 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.
Pharmacokinetic properties
After oral administration, praziquantel is almost completely absorbed from the intestinal tract. After absorption, the drug is widely distributed in the organism, metabolised into inactive forms in the liver and secreted in bile. It is excreted within 24 hours to more than 95% of the administered dosage.
The embonate salt of pyrantel has low aqueous solubility, an attribute that reduces absorption from the gut and allows the drug to reach and be effective against parasites in the large intestine. Following absorption, pyrantel embonate is quickly and almost completely metabolised into inactive components which are rapidly excreted in the urine.
Febantel is an inactive pro-drug which is absorbed and then metabolised relatively rapidly to a number of metabolites, including fenbendazole and oxfendazole, which have anthelmintic activity.
Following the single oral administration of this veterinary medicinal product the maximum plasma concentrations of praziquantel, pyrantel, fenbendazole and oxfendazole were found 327, 81, 128 and 165 ng/ml and were obtained after 2.2, 4.5, 5.2 and 6.3 hours.