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Pharmacological particulars
Pharmacodynamic properties
Indoxacarb is an ectoparasiticide belonging to the oxadiazine chemical family. Indoxacarb is a pro-drug that requires bioactivation by enzymes in susceptible insects to exert its pharmacodynamic effects. It enters the insect primarily through ingestion but is also absorbed, to a lesser degree, through the insect cuticle. In the mid-gut of susceptible insect species, the insect’s enzymes remove the carbomethoxy group from parent indoxacarb, and convert it into its biologically active form. The bioactivated metabolite acts as a voltage-dependent sodium channel antagonist in insects, by blocking the sodium channels that regulate the flow of sodium ions in the insect’s nervous system. This results in a rapid cessation of feeding within 0 to 4 hours after treatment followed by cessation of egg laying (oviposition), paralysis and death occurring within 4 to 48 hours. In addition to its adulticidal activity against fleas, indoxacarb has activity against the developing stages of fleas in the immediate surroundings of the treated dog.
Permethrin belongs to the Type I class of pyrethroids, which are acaricides and insecticides with repellent activity. Pyrethroids affect the voltage-gated sodium channels in vertebrates and non-vertebrates. Pyrethroids are so-called “open channel blockers” affecting the sodium channel by slowing both the activation and the inactivation properties, thus leading to hyper-excitability and death of the parasite.
The product provides repellent (anti-feeding) activity against ticks and various insect species, preventing the repelled parasite from taking a blood meal and thus reducing the risk of disease transmission.
Pharmacokinetic properties
Following a single spot-on application of the product, indoxacarb and permethrin can still be detected in both skin and hair coat after 4 weeks post-treatment. Absorption through the skin also occurs, but this systemic absorption is partial and not relevant for the clinical efficacy. The absorbed indoxacarb and permethrin are extensively metabolised by the liver to a variety of metabolites. The major route of excretion is in faeces for indoxacarb and both in urine and faeces for permethrin.