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Onset and duration of action of lokivetmab in a canine model of IL‐31 induced pruritus
BACKGROUND: Interleukin (IL)‐31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL‐31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs. OBJECTIVE: To...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291138/ https://www.ncbi.nlm.nih.gov/pubmed/33830571 http://dx.doi.org/10.1111/vde.12943 |
Sumario: | BACKGROUND: Interleukin (IL)‐31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL‐31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs. OBJECTIVE: To assess the onset of action and duration of effect of lokivetmab (Cytopoint) in the IL‐31‐induced pruritus model. ANIMALS: Twenty‐four purpose‐bred beagle dogs (neutered males, spayed and intact females) 1.5–4.7 years old and weighing between 6 and14 kg. METHODS AND MATERIALS: Randomized, blinded, placebo‐controlled studies were designed to evaluate the antipruritic properties of lokivetmab. Laboratory beagle dogs were given either placebo, 0.125, 0.5 or 2.0 mg/kg lokivetmab, subcutaneously. IL‐31 then was administered to evaluate pruritus 3–5 h post‐placebo or ‐lokivetmab administration as well as one, seven, 14, 28, 42 and 56 days post‐dosing. Pruritus was evaluated over a 2 h window in animals by video monitoring and scored using a categorical scoring system. RESULTS: When animals were given 2.0 mg/kg lokivetmab, a significant reduction in pruritus was observed at 3–4, 4–5 and 3–5 h post‐treatment (P ≤ 0.0001). When animals were given either 0.125, 0.5 or 2 mg/kg lokivetmab, the duration of effect was dose‐dependent and statistically significant for 14, 28 and 42 days, respectively (P ≤ 0.0288). CONCLUSION: These data indicate that a single subcutaneous injection of 2 mg/kg lokivetmab produces a significant suppression of pruritus starting 3 h post‐treatment that can be sustained for 42 days. |
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