Avaliação farmacocinética de nanocápsulas contendo meloxicam em cadelas submetidas à ovariohisterectomia

Abstract

The treatment of pain in animals is essential to ensure the comfort and well-being of patients, based on the use of drugs with anti-inflammatory and analgesic properties. In this context, meloxicam (MLX) has been widely used in the treatment of musculoskeletal pain and chronic pain and as an adjuvant in pre- and postoperative management. However, innovative formulation strategies have been investigated to improve efficacy and reduce possible adverse effects. In this sense, nanocapsules (NCs) are an interesting strategy to improve the physicochemical aspects of drugs, increase efficacy and reduce adverse effects. The aim of the study was to evaluate the pharmacokinetics (PK) of MLX (0.2 mg/kg) in female dogs submitted to ovariohysterectomy. The NCs were prepared by the preformed polymer interfacial deposition method and characterized. Plasma samples were collected and quantified by a bioanalytical method. Non-compartmental PK (NCA) was performed using the PKanalix software (Monolix® – Lixoft) and the following parameters were evaluated: AUC, Cmax, Tmax, Vd, t1/2, CL, MRT. In addition to the NCA analysis, a population pharmacokinetic modeling (PopPK) was also carried out, developed in the Monolix® – Lixoft software, testing different structural and statistical models. PK NCA results showed that NCs increased Vd, t1/2, and a slight increase in Tmax of MLX. A two-compartment model with a transit compartment was used to describe the MLX PK, where the NCs were covariates in the absorption constant and in the Vd. In addition, the age of the animals influenced the clearance. A PopPK model was successfully developed, capable of describing the MLX PK in plasma from female dogs submitted to ovariohysterectomy surgery. NCs have been shown to be therapeutically promising for the treatment of pain in animals.