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Pharmacological particulars
ATCvet code: QP54AB51.
Afoxolaner is an insecticide and acaricide belonging to the isoxazoline family. Afoxolaner acts as an antagonist at ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA). Isoxazolines, among the chloride channel modulators, bind to a distinct and unique target site within the insect GABACls, thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. The selective toxicity of afoxolaner between insects, acarines and mammals may be inferred by the differential sensitivity of the insects and acarines’ GABA receptors versus mammalian GABA receptors.
It is active against adult fleas as well as against several tick species such as Rhipicephalus sanguineus, Dermacentor reticulatus and D. variabilis, Ixodes Ricinus, Ixodes hexagonus and I. scapularis, Amblyomma americanum, Haemaphysalis longicornis, and Hyalomma marginatum.
Afoxolaner kills fleas before egg production and therefore prevents the risk of household contamination. It can be used as part of a treatment strategy for the control of flea allergy dermatitis (FAD).
Milbemycin oxime:
Milbemycin oxime is an antiparasitic endectocide belonging to the group of macrocyclic lactones. Milbemycin oxime contains two major factors, A3 and A4 (ratio of 20:80 for A3:A4). It is a fermentation product of Streptomyces milbemycinicus. Milbemycin oxime acts by disrupting the glutamate neuro-transmission in invertebrates. Milbemycin oxime increases glutamate binding with consequent enhanced chloride ion flow into the cell. This leads to hyperpolarisation of the neuromuscular membrane resulting in paralysis and death of the parasites.
Milbemycin oxime is active against several gastrointestinal worms (Toxocara canis, Toxascaris leonina, Ancylostoma caninum, Ancylostoma braziliense, Ancylostoma ceylanicum, Trichuris vulpis), the adults and immature adults (L5) of lungworm Angiostrongylus vasorum and heartworm (Dirofilaria immitis larvae).
The systemic absorption of afoxolaner is high. The absolute bioavailability is 88 %. The mean maximum concentration (Cmax) is 1,822 ± 165 ng/ml in plasma found 2–4 hours (Tmax) after a 2.5 mg/kg afoxolaner dose.
Afoxolaner distributes into tissues with a volume of distribution of 2.6 ± 0.6 l/kg and a systemic clearance value of 5.0 ± 1.2 ml/h/kg. The terminal plasma half-life is approximately 2 weeks in dogs.
Milbemycin oxime plasma concentrations peak quickly within the first 1–2 hours (Tmax) indicating that absorption from the chewable tablets is fast. The absolute bioavailability is 81 % and 65 % for the A3 and A4 forms, respectively. The terminal half-lives and maximum concentrations (Cmax) following oral administration are 1.6 ± 0.4 days and 42 ± 11 ng/ml for the A3 form, 3.3 ± 1.4 days and 246 ±71 ng/ml for the A4 form.
Milbemycin oxime distributes into tissues with a volume of distribution of 2.7 ± 0.4 l/kg and 2.6 ± 0.6 l/kg for the A3 and A4 forms, respectively. Both forms have low systemic clearance (75 ± 22 ml/h/kg for the A3 form and 41 ± 12 ml/h/kg for the A4 form).