Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration

Abstract

BackgroundFluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies.MethodsSixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment.ResultsNo adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose.ConclusionsFluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration.

Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases

“…Even though these compounds have neuronal targets (Fig. 1A), they have been generally shown to be safe in mammals, as they show limited brain penetration (14) and significant selectivity for insect over mammalian receptors (12,15). Herein we evaluate two representatives of this compound class in multiple disease-carrying vector species and support the case for their potential use as human oral vector-control drugs.…”

Uso do fluralaner no tratamento da demodicidose canina juvenil generalizada: relato de caso

“…Nesses animais, devido a uma mutação no gene autossômico recessivo MDR1, há uma produção de glicoproteínas P defeituosas, o que permite que o medicamento ultrapasse a barreira hematoencefálica, provocando, consequentemente, graves repercussões sistêmicas, incluindo o óbito do paciente (Andrade, 2015;Delayte, 2016). Isso não seria um problema relacionado ao fluralaner, já que foi demonstrada ausência de toxicidade quando administrado três vezes acima da dose máxima recomendada em cães da raça Collie, sabidamente portadores da mutação do gene MDR1 (Walther et al, 2014b).…”

A field trial in Thailand of the efficacy of oral fluralaner for the treatment of dogs with generalized demodicosis

“…In field studies involving naturally infested dogs, a single oral dose of fluralaner proved to be >99% effective against fleas and ticks over a period of 12 weeks following treatment . Isoxazolines are safe for dogs with the ABCB1‐ Δ 1 (MDR‐1) mutation associated with neurological adverse effects of macrocyclic lactones . Two studies have reported the efficacy of fluralaner for the treatment of canine generalized demodicosis, both showing that fluralaner can decrease the number of Demodex mites by 100% after 2 months …”