Topical and oral emodepside formulations for last-line treatment of multianthelmintic drug-resistant hookworms when given orally to dogs are not bioequivalent.
Theresa A Quintana, Greta N Karwath, Erin J Mayhue, Maria C Jugan, Jeba R J Jesudoss Chelladurai, Stephanie E Martinez
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引用次数: 0
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.
期刊介绍：
The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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