Pharmacodynamic properties
Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. Fipronil and its metabolite fipronil sulfone act at ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA) as well as desensitising (D) and non-desensitising (N) channels gated by glutamate (Glu, unique invertebrate ligand-gated chloride channels), thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. This results in uncontrolled activity of the central nervous system and death of insects or acari.
Pyriproxyfen is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues. Pyriproxyfen sterilises adult fleas and inhibits the development of immature stages. The molecule prevents, by contact, the emergence of adult insects by blocking the development of eggs (ovicidal effect), larvae and pupae (larvicidal effect), which are subsequently eliminated. Following contact and/or ingestion by adult fleas, the molecule also acts by sterilising eggs during their maturation and before being laid. The molecule prevents contamination of the environment of treated animals with the immature stages of fleas.
Combination of fipronil and pyriproxyfen provides an insecticidal and acaricidal activity against fleas (Ctenocephalides felis), ticks (Rhipicephalus turanicus, Ixodes ricinus) in addition to preventing flea eggs developing into adult fleas.
Such combination provides an integrated flea control which can be used against infestations with fleas alone or in association with ticks.
Pharmacokinetic particulars
Following topical application of the product, under the normal conditions of use, fipronil and pyriproxyfen are well distributed in the haircoat of the cat from the first day post application. The major metabolite of fipronil is the sulfone derivative, which also possesses insecticidal and acaricidal properties.
The concentrations of fipronil and pyriproxyfen in the haircoat decrease over time but both active substances are present for at least 84 days after application (i.e. above the lower limit of quantification (LOQ) 100 ng/g for fipronil and 50 ng/g for pyriproxyfen). Concentrations of fipronil sulfone remained below the lower limit of quantification (LOQ 100 ng/ml) after product application.
The plasmatic peaks of fipronil and pyriproxyfen concentration are rapidly reached 1 day after administration. Concentrations of fipronil are quantifiable in all cats up to 3 days after application (LOQ 1 ng/ml). Concentrations of pyriproxyfen are quantifiable in all cats up to 42 days after application (LOQ 0.2 ng/ml). Concentrations of fipronil sulfone remained below the lower limit of quantification (LOQ 1 ng/ml) after product application.