“
“Advances in research for ectoparasitological control have brought new therapeutic drugs forward for clinical usage (e.g., fipronil, imidacloprid and spinosad) (Beugnet and Franc, 2012). trans-isomer price Afoxolaner is a compound from a new structurally unique isoxazoline class which acts as a novel and specific blocker of insect ligand-gated chloride ion channels (Shoop et al., 2014). It was formulated in a unique soft, beef-flavored chew (Nexgard®, Merial). There are four

chew sizes, of respectively 0.5 g, 1.25 g, 3 g and 6 g, containing 11.3 mg, 28.3 mg, 68 mg and 136 mg of afoxolaner. They are intended for dogs weighing 2–4 kg, 4.1–10 kg, 10.1–25 kg and 25.1–50 kg, respectively. The weight bands of the various chew sizes can result in a minimum therapeutic dose of 2.5 mg/kg and a maximum exposure dose of 6.3 mg/kg body weight. The assessment of the safety of a compound in the target species is a prerequisite for registration of veterinary products. The guidelines for target animal safety studies now require that the compound be tested using the final commercial formulation at 1, 3, and 5 times the maximum exposure dose (VICH,

2008). Oral as well as topically applied antiparasitic drugs are usually manufactured so that one size tablet/chewable or pipette can be administered to animals within a specified weight range (Blagburn et al., 2010). Erlotinib cell line The dose received by the heaviest animal in the range is designated many as the minimum therapeutic dose. The dose received by the lightest animal in the range is designated the maximum

exposure dose. The maximum exposure dose must then be multiplied by 1, 3, and 5 times. The regulatory guidelines also determine the number of times a formulation must be administered during the study and in addition to the minimum age of animals to be tested. The formulation is recommended to be administered monthly for six treatments. If a product is designed for use in young animals, the age of the animal tested must be the minimum age for which the commercial product will be used. Establishment of safety for use in the target species and for animal at a minimum age is mandatory to get a registration as veterinary medicine. It is necessary to demonstrate to the veterinarians and the pet owners that no unexpected adverse event will occur in treated dogs. Therefore, the objective of this study was to determine the safety profile of afoxolaner administered in a soft chewable formulation to 8-week-old dogs at either 1×, 3× or 5× the maximum exposure dose (i.e., 6.3 mg/kg, 18.9 mg/kg and 31.5 mg/kg) at three, one-month-dose-intervals followed by three, 2-week-dose intervals.