Topical and oral emodepside formulations for last-line treatment of multianthelmintic drug-resistant hookworms when given orally to dogs are not bioequivalent.

Abstract

OBJECTIVE: To evaluate the pharmacokinetics of emodepside in dogs following single-dose administration of the FDA-approved feline topical solution orally and topically and the European Medicines Agency-approved canine modified-release tablet orally and to assess the bioequivalence of the feline topical solution administered orally compared to the canine modified-release tablet. METHODS: This study was conducted in 3 phases, during which dogs received single doses of emodepside as the feline topical solution (1 mg/kg) orally, the canine modified-release tablet (1 mg/kg) orally, and the topical feline solution (3 mg/kg) topically. Plasma pharmacokinetic profiles were determined for 21 days postdose. Bioequivalence testing was conducted for orally administered emodepside. RESULTS: 7 healthy client-owned dogs (4 female and 3 male) were prospectively enrolled in this crossover study from May through August 2023. Oral administration of the feline topical solution resulted in markedly greater emodepside absorption than the modified-release tablet and was not bioequivalent. Emodepside plasma concentrations following topical administration of the FDA formulation were 36- to 122-fold lower than after oral administration. CONCLUSIONS: The feline topical solution administered orally at 1 mg/kg is not bioequivalent to the canine modified-release tablet. Markedly higher absorption of the feline topical solution administered orally raises potential safety concerns for extralabel use in dogs to treat multianthelmintic drug-resistant hookworm infections. Poor absorption following topical administration suggests it may be unsuitable for treating multianthelmintic drug-resistant hookworm infections. CLINICAL RELEVANCE: These findings highlight potential emodepside toxicity risks with extralabel use of the FDA-approved topical feline product and help inform safe off-label use in dogs.