Pharmacotherapeutic group: Ectoparasiticides for topical use, incl. insecticides
ATCvet code: QP53AX65
Fleas from pets often infest the animal's basket, bedding and regular resting areas such as carpets and soft furnishings which should be treated, in case of massive infestation and at the beginning of the control measures, with a suitable insecticide and vacuumed regularly.
No data on the effect of bathing/shampooing on the efficacy of the product in cats are available. However, based on information available for dogs shampooed as from 2 days after application of the product, it is not recommended to bath animals within 2 days after application of the product.
Fipronil is an insecticide and acaricide belonging to the phenylpyrazole family. It acts by interacting with ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), 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 acarines. Fipronil kills fleas within 24 hours and ticks (Dermacentor variabilis, Rhipicephalus sanguineus, Ixodes ricinus, ) and lice within 48 hours post-exposure.
(S)-Methoprene is an insect growth regulator (IGR) of the class of compounds known as juvenile hormone analogues that inhibit the development of immature stages of insects. This compound mimics the action of juvenile hormone and causes impaired development and death of the developing stages of fleas. The on-animal ovicidal activity of (S)-methoprene results from either direct penetration of the eggshell of newly laid eggs or from absorption through the cuticle of the adult fleas. (S)-methoprene is also effective in preventing flea larvae and pupae from developing, which prevents contamination of the environment of treated animals with the immature stages of fleas.
Studies of metabolism of fipronil have demonstrated that the major metabolite is the sulfone derivative of fipronil.
(S)-methoprene is extensively degraded into carbon dioxide and acetate that are subsequently incorporated into endogenous materials.
The pharmacokinetic profiles after topical application of fipronil and (S)-methoprene in combination were studied in cats in comparison to intravenous dosing of fipronil or (S)-methoprene alone. This established absorption and other pharmacokinetic parameters under conditions mimicking clinical practice. The topical application, with additional potential oral exposure from licking, resulted in overall systemic absorption of fipronil (18%) with a mean maximum concentration(Cmax) of approximately 100 ng/ml fipronil and 13 ng/ml of fipronil sulfone in plasma.
Peak fipronil plasma concentrations are rapidly attained (mean tmax approximately 6 h) and decline with a mean terminal half-life of approximately 25 h.
Fipronil is slightly metabolised to fipronil sulfone in cats.
Plasma concentrations of (S)-methoprene were generally below the limit of quantitation (20 ng/ml) in cats after topical application.
Both (S)-methoprene and fipronil, together with its major metabolite, are well-distributed in the hair/coat of cats within one day after application. The concentrations of fipronil, fipronil sulfone and (S)-methoprene in the hair/coat decrease with time and are detectable for at least 59 days after dosing. Parasites are killed through contact rather than by systemic exposure.
No pharmacological interaction between fipronil and (S)-methoprene was noted.