Le méthotrexate chez le chien et le cheval : études pharmacocinétiques et perspectives cliniques
摘要：
Methotrexate is widely used in humans at low doses, once weekly, as an immunomodulating and anti-inflammatory drug. This drug may be an interesting therapeutic alternative for the management of autoimmune or hypersensitivity diseases in pets or horses. The main objective of our study is to evaluate its tolerance in dogs and horses, and to study its pharmacokinetic characteristics to determine an appropriate dosing regimen for each species. Our results show that methotrexate is well tolerated in animals. In dogs, mild adverse effects (anorexia or even vomiting or diarrhea) and intermittent elevations of liver enzymes are observed. In horses, the only adverse effects reported are elevations in liver enzymes, reversible upon discontinuation of treatment. Oral bioavailability is much lower than subcutaneous bioavailability, and less than 1 % in horses. The methotrexate clearance in dogs is slightly higher than in humans. In horses, reduced clearance and metabolism lead to a recommendation for lower doses. We suggest 0.2 mg/kg/week, which will have to be confirmed by clinical trials. Our second objective is to evaluate the efficacy of methotrexate in the treatment of atopic dermatitis in dogs in a double-blind Phase III clinical trial. Animal recruitment is still ongoing. The first results obtained on 6 dogs, however, are satisfactory in terms of clinical response to a dosage ranging from 0.25 to 0.5 mg/kg/week subcutaneously
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