Estudio farmacocinético de cefonicid en la especie caprina

Résumé

The pharmacokinetics of cefonicid were studied in goats after intravenous, intramuscular and subcutaneous administration to healthy animals at a dose of 10 mg/kg and after subcutaneous administration of a long-acting gel formulation with poloxamer P407 and 2-hydroxipropil- -cyclodextrin at 20 mg/kg bodyweight. The purpose of this investigation was to characterize the pharmacokinetic profile of this antibiotic in these species, as well as its potential penetration in milk. The cefonicid plasma concentrations were determined by an HPLC method with ultraviolet detection. Plasma concentration-time data after each type of administration were fitted to compartmental and non-compartmental models using different software such as MULTIFIT and WinNonlin Professional, respectively. All administrations could best be described by one compartmental open model. After intravenous administration, terminal half-life (t½?z) and mean residence time (MRT) were 0,213 0,027 h and 0,268 0,051 h, respectively. The volumen of distribution calculated by the area method (Vz) was 0,174 0,03 L/kg and that at steady-state (Vss) was 0,141 0,023 L/kg indicating a moderate body distribution. Total body clearance (Cl) was 0,531 0,073 L/kg·h suggesting a rapid elimination of cefonicid from plasma. After intramuscular and subcutaneous administrations, terminal half-lives of 0.433 0.05 h and 0.576 0.149 h, and MRT values of 0.799 0.177 h and 0.982 0.288 h were obtained, respectively. After subcutaneous administration of the long-acting gel formulation t½?z was 1,235 0,167 h and MRT 1,984 0,175 h. The data showed a greater permanence of cefonicid in the body after subcutaneous administration of the long-lasting formulation, as well as a slower absorption rate than by the other routes. Mean cefonid bioavailability gave values of F = 75,34 11,28 % and F= 71,09 19,14% after intramuscular and subcutaneous administrations, respectively. After subcutaneous administration of the long-lasting formulation, the bioavailability was 102,84 15,157 wich implies a better absorption than by the other extravacular routes. Concerning to the study of milk, no concentrations of cefonicid above the quantification limit of the technique were obtained in any sample, which demonstrates its poor disposition in this fluid and its potential use in lactating goats since no residues will be generated. A dosage regimen for cefonicid has been established based on the pharmacokinetic/pharmacodynamic integration considering T>MIC and with a fixed value of MIC of 2 mg/L. For intramuscular and subcutaneous administration routes, can be established a dosage interval every 4 hours while, for the subcutaneous route with long-lasting formulation, the dose interval can be increased two times until 8 hours.