Plasma pharmacokinetic profile of fluralaner (Bravecto™) and ivermectin following concurrent administration to dogs

Abstract Background Fluralaner is a novel systemic ectoparasiticide for dogs providing immediate and persistent flea, tick and mite control after a single oral dose. Ivermectin has been used in dogs for heartworm prevention and at off label doses for mite and worm infestations. Ivermectin pharmacokinetics can be influenced by substances affecting the p-glycoprotein transporter, potentially increasing the risk of ivermectin neurotoxicity. This study investigated ivermectin blood plasma pharmacokinetics following concurrent administration with fluralaner. Findings Ten Beagle dogs each received a single oral administration of either 56 mg fluralaner (Bravecto™), 0.3 mg ivermectin or 56 mg fluralaner plus 0.3 mg ivermectin/kg body weight. Blood plasma samples were collected at multiple post-treatment time points over a 12-week period for fluralaner and ivermectin plasma concentration analysis. Ivermectin blood plasma concentration profile and pharmacokinetic parameters Cmax, tmax, AUC∞ and t½ were similar in dogs administered ivermectin only and in dogs administered ivermectin concurrently with fluralaner, and the same was true for fluralaner pharmacokinetic parameters. Conclusions Concurrent administration of fluralaner and ivermectin does not alter the pharmacokinetics of either compound. Based on the plasma pharmacokinetic profile and the clinical observations, there is no evident interaction between fluralaner and ivermectin, and co-administration does not increase the risk of ivermectin associated neurotoxicity

Fluralaner activity against life stages of ticks using Rhipicephalus sanguineus and Ornithodoros moubata IN in vitro contact and feeding assays

Abstract Background Fluralaner is a novel isoxazoline eliciting both acaricidal and insecticidal activity through potent blockage of GABA- and glutamate-gated chloride channels. The aim of the study was to investigate the susceptibility of juvenile stages of common tick species exposed to fluralaner through either contact (Rhipicephalus sanguineus) or contact and feeding routes (Ornithodoros moubata). Methods Fluralaner acaricidal activity through both contact and feeding exposure was measured in vitro using two separate testing protocols. Acaricidal contact activity against Rhipicephalus sanguineus life stages was assessed using three minute immersion in fluralaner concentrations between 50 and 0.05 μg/mL (larvae) or between 1000 and 0.2 μg/mL (nymphs and adults). Contact and feeding activity against Ornithodoros moubata nymphs was assessed using fluralaner concentrations between 1000 to 10−4 μg/mL (contact test) and 0.1 to 10−10 μg/mL (feeding test). Activity was assessed 48 hours after exposure and all tests included vehicle and untreated negative control groups. Results Fluralaner lethal concentrations (LC50, LC90/95) were defined as concentrations with either 50%, 90% or 95% killing effect in the tested sample population. After contact exposure of R. sanguineus life stages lethal concentrations were (μg/mL): larvae - LC50 0.7, LC90 2.4; nymphs - LC50 1.4, LC90 2.6; and adults - LC50 278, LC90 1973. After exposure of O. moubata nymphs to fluralaner lethal concentrations were (μg/mL): contact exposure - LC50 720, LC95 1133; and feeding exposure- LC50 0.00007, LC95 0.09. Conclusions Fluralaner demonstrates potent in vitro acaricidal activity against all life stages of the brown dog tick, R.sanguineus. The testing of fluralaner contact and feeding routes using O. moubata nymphs demonstrates a high acaricidal activity in both exposure routes

The effect of food on the pharmacokinetics of oral fluralaner in dogs

BACKGROUND: Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. The pharmacokinetics of orally administered drugs may be influenced by feeding. This study investigated the influence of concurrent feeding on fluralaner pharmacokinetics. METHODS: Twelve fasted or fed beagles received a single oral administration of 25 mg fluralaner/kg body weight in a chewable tablet. Plasma samples were collected at multiple post-treatment time points for fluralaner concentration analysis. Clinical observations were performed on all dogs at regular intervals throughout the study. RESULTS: Fluralaner was readily absorbed in fasted and fed dogs administered at a dose of 25 mg/kg BW with a similar mean t(max) for both groups. In fed dogs, AUC and C(max) were increased compared to fasted dogs by a factor of 2.5 and 2.1 respectively. The difference in AUC and C(max) between the fed and fasted groups was statistically significant. No adverse events were observed following oral fluralaner administration to fasted and fed dogs. CONCLUSIONS: Fluralaner is absorbed to a considerable extent in fasted and fed dogs. Administration of fluralaner chewable tablets with food significantly increases bioavailability