Abstract
BACKGROUND: Studies reported here were conducted to evaluate the safety and effectiveness of advantus (imidacloprid) soft chewable tablets for the treatment of flea (Ctenocephalides felis) infestations on dogs and puppies 10 weeks of age or older and weighing 4 pounds or greater. METHODS: A pharmacokinetic study was conducted to evaluate parameters of orally administered imidacloprid. A dose confirmation study was conducted to confirm the efficacy of 0.75 mg/kg at 8, 12 or 24 hours post-treatment. A knockdown and speed of kill study was conducted to confirm the efficacy of 0.75 mg/kg dose at 0.5, 1, 4 or 24 hours post-treatment. The safety of a daily dose administered for six months at approximately 1, 3, and 5 times the maximum exposure dose of 3.75 mg/kg was evaluated in puppies. A field study was conducted to evaluate the safety and efficacy of a daily oral dose of 0.75 mg/kg for 14 days in client-owned dogs. RESULTS: The pharmacokinetic parameters of the final imidacloprid oral formulation were; Tmax 1.31 hours, Cmax 690.0 ng/mL, AUC 2615.5 h*ng/mL and half-life was 2.2 hours. The efficacy of 0.75 mg/kg BW was 98.6%, 99.9% and 100% at 8, 12 and 24 hours post-treatment, respectively. The live flea counts were significantly different (p < 0.0001) and the treatment was well tolerated. The flea counts at 1 hour post-treatment were significantly lower in the treated group and the speed of kill efficacy was 96.6% at 4 hours post-treatment in the knockdown and speed of kill study. The target animal safety study showed that the advantus soft chewable tablets administered orally to 10-week-old puppies once daily for 6 months at approximately 1, 3 and 5 times the maximum dose of 3.75 mg/kg was well tolerated and did not produce clinically relevant findings in Beagles. In the field study, efficacy of the soft chewable tablets administered daily for 14 days to flea-infested dogs was 98.2%. CONCLUSION: Imidacloprid administered orally as a soft chewable tablet for the treatment of fleas on dogs was safe and highly effective with a rapid knockdown effect and rapid elimination.