ATCvet code: QP54AB52
Pharmacodynamic properties
Fluralaner
Fluralaner is an acaricide and insecticide. It is efficacious against ticks (Dermacentor reticulatus, Ixodes hexagonus, I. ricinus and Rhipicephalus sanguineus), and fleas (Ctenocephalides canis and C. felis) on the dog.
For fleas, the onset of efficacy is within 24 hours of attachment, for 30 days after the veterinary medicinal product’s administration.
Fluralaner reduces the risk of infection with Babesia canis canis via transmission by Dermacentor reticulatus by killing the ticks within 36 hours, before disease transmission occurs.
Fluralaner reduces the risk of infection with D. caninum via transmission by C. felis by killing the fleas within 24 hours, before disease transmission occurs.
Fluralaner has a high potency against ticks and fleas by exposure via feeding, i.e., it is systemically active on target parasites.
Fluralaner is a potent inhibitor of parts of the arthropod nervous system by acting antagonistically on ligand-gated chloride channels (GABA-receptor and glutamate-receptor).
In molecular on-target studies on insect GABA-receptors of flea and fly, fluralaner is not affected by dieldrin resistance.
In vitro, using a variety of different bio-assays, fluralaner was not affected by proven field resistances against amidines (tick), organophosphates (tick), cyclodienes (tick, flea), macrocyclic lactones, phenylpyrazoles (tick, flea), benzophenyl ureas (tick), pyrethroids (tick) and carbamates (tick).
Newly emerged fleas on a dog are killed before viable eggs are produced. An in-vitro study demonstrated that very low concentrations of fluralaner also stop the production of viable eggs by fleas. The flea life cycle is therefore broken.
New flea infestations are prevented by the rapid onset of action and long-lasting efficacy against adult fleas on the animal and the absence of viable egg production. The veterinary medicinal product therefore also contributes towards the control of environmental flea populations in areas to which treated dogs have access.
Moxidectin
Moxidectin, a semisynthetic derivative of nemadectin, belongs to the milbemycin group of macrocyclic lactones (avermectins being the other). Milbemycins and avermectins have a common mode of action that is based on the binding of ligand-gated chloride channels (glutamate-R and GABA-R). This leads to an increased membrane permeability of nematode and arthropod nerve and/or muscle cells for chloride ions and results in hyperpolarisation, paralysis and death of the parasites. Binding of glutamate-gated chloride channels, which are specific to invertebrates and do not exist in mammals, is considered the main mechanism for the anthelmintic and insecticidal activity. Moxidectin has parasiticidal activity against a range of internal and external parasites (including nematodes (Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala), lungworm (Angiostrongylus vasorum) and heartworm (Dirofilaria immitis)). Moxidectin lacks substantial efficacy against fleas and ticks.
Pyrantel
Pyrantel belongs to the class of tetrahydropyrimidines and targets nicotinic acetylcholine channel receptors (nAChRs). Selectivity of pyrantel for invertebrate nAChRs is based on high-affinity binding to specific nematode receptor subtypes and a subsequent agonistic mode of action leading to a depolarizing neuromuscular block, which causes muscle contraction, paralysis, and subsequently death of the parasites. Pyrantel lacks activity against muscarinic mAChRs. Pyrantel is an anthelmintic with parasiticidal activity against gastrointestinal parasites (including T. canis, T. leonina, A. caninum and U. stenocephala).
Pharmacokinetic particulars
Fluralaner is readily and rapidly absorbed systemically following oral dosing, reaching mean maximum concentrations in plasma within 17.7 hours (Tmax) after administration.
Fluralaner is slowly eliminated from plasma (half-life of approximately 12 days) via biliary excretion and elimination through the faeces with minor contributions of metabolic clearance. A fed prandial state of the dog increases the extent of absorption of fluralaner.
Moxidectin is readily and rapidly absorbed systemically following oral dosing, reaching mean maximum concentrations in plasma within 3 hours (Tmax) after administration. Moxidectin is slowly eliminated from plasma (half-life of approximately 16 days) via biliary excretion and elimination through the faeces with minor contributions of metabolic clearance.
Pyrantel is poorly absorbed, and the absorbed portion has a Tmax of 1.5 hours and half-life of 6 hours. Pyrantel is eliminated through faeces and the small, absorbed portion is eliminated mainly via urine.
The pharmacokinetic profiles of fluralaner, moxidectin and pyrantel are not affected by co-administration.
No accumulation of pyrantel was observed after six repeated monthly administrations of the veterinary medicinal product at the maximum recommended dose. However, accumulation of fluralaner was observed up to and including the 6th monthly administration. Additionally, accumulation of moxidectin was observed up to and including the 5th monthly administration.