Prolonged fecal elimination of isoxazoline antiparasitic drugs in dogs and cats: is there a risk for nontarget species?

Isoxazoline antiparasitic drugs are a new class of ectoparasiticides used in veterinary medicine for companion animals. Four active substances-fluralaner, (es)afoxolaner, lotilaner, and sarolaner-are marketed globally for flea and tick control. Isoxazolines exhibit long plasma half-lives in dogs and cats, with lotilaner reaching 30 days and sarolaner up to 41.5 days in cats. Their bioavailability varies with feeding; fasting significantly reduces lotilaner absorption. These drugs are primarily eliminated via the biliary/fecal route, with fluralaner showing a fecal elimination half-life of 3 to 12 days in felids and 6 to 38 days in canids. The European Medicines Agency has highlighted the risk of these substances contaminating ecosystems, though data on their environmental release are limited. Recent studies suggest that fluralaner and other parasiticides can be transferred to the environment via feces, urine, or pet hair. This study examined isoxazoline fecal elimination in dogs and cats. Elimination half-lives were determined in groups of five dogs or five cats per active substance. All animals received the drug according to label instructions. The estimated median half-lives were 15.5 and 22.0 days for fluralaner and lotilaner in cats, and 22.9, 24.6, 19.7, and 17.4 days for fluralaner, lotilaner, afoxolaner, and sarolaner in dogs, respectively. Fluralaner and lotilaner were still detected in feces after the end of the recommended treatment period. We used Monte Carlo simulations to assess the risk to nontarget arthropods. Environmental risk assessment indicated that dung-feeding insects could be highly exposed to isoxazoline parasiticides, with fluralaner and lotilaner having the greatest potential impact. These findings emphasize the need for further research on environmental contamination (pathways, quantitative estimate) and impact of veterinary parasiticides on nontarget species.