The intravenous and oral pharmacokinetics of lotilaner in dogs

BACKGROUND: Lotilaner is a new oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in dogs. It is formulated as pure S-enantiomer in flavoured chewable tablets (Credelio™). The pharmacokinetics of lotilaner were thoroughly determined after intravenous and oral administration and under different feeding regimens in dogs. METHODS: Twenty-six adult beagle dogs were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration of 20 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. The effects of timing of offering food and the amount of food consumed prior or after dosing on bioavailability were assessed in a separate study in 25 adult dogs. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability was evaluated in an analytical study. RESULTS: Following oral administration in fed animals, lotilaner was readily absorbed and peak blood concentrations reached within 2 hours. The terminal half-life was 30.7 days. Food enhanced the absorption, providing an oral bioavailability above 80% and reduced the inter-individual variability. Moreover, the time of feeding with respect to dosing (fed 30 min prior, fed at dosing or fed 30 min post-dosing) or the reduction of the food ration to one-third of the normal daily ration did not impact bioavailability. Following intravenous administration, lotilaner had a low clearance of 0.18 l/kg/day, large volumes of distribution V(z) and V(ss) of 6.35 and 6.45 l/kg, respectively and a terminal half-life of 24.6 days. In addition, there was no in vivo racemization of lotilaner. CONCLUSIONS: The pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (Credelio™) were studied in detail. With a T(max) of 2 h and a terminal half-life of 30.7 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least 1 month. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-017-2475-z) contains supplementary material, which is available to authorized users.