Farmacocinética y biodisponibilidad de ceftiofur sódico en caprinos

Resumen Se determinaron parametros farmacocineticos de ceftiofur sodico con dosis unica de 2.2 mg/kg por via intravenosa e intramuscular, en un diseno cruzado de tratamiento en hembras caprinas adultas no gestantes (n= 6). Las concentraciones plasmaticas en funcion del tiempo se determinaron por el metodo microbiologico de difusion en agar utilizando medio Mueller-Hinton y Providencia alcalifaciens, cuyo limite de cuantificacion se establecio en 0.039 μg/ml. Los datos de concentracion plasmatica de ceftiofur en funcion del tiempo se analizaron por el modelo farmacocinetico no compartimental utilizando el sofware PK Solution 2.0. Los parametros obtenidos para la via intravenosa fueron: vida media de eliminacion (t 1/2 B ) = 1.63 ± 0.04 horas, clearance total (Cl tot ) = 3.3 ± 1.1 ml/kg/min, volumen de distribucion (Vd ss ) = 0.38 ± 0.19 L/kg, area bajo la curva (ABC) = 716.5 ± 225.5 μg/min/ml. Estos valores no difieren significativamente de los obtenidos del ensayo intramuscular (p max ) de 3.6 ± 0.5 μg/ml, con un tiempo maximo (t max ) de 0.53 ± 0.31 horas y elevada biodisponibilidad (97.6 ± 0.1%). Los resultados indican que la aplicacion intramuscular provee rapida absorcion y optima biodisponibilidad, generando niveles plasmaticos que exceden la concentracion inhibitoria minima (CIM) de patogenos respiratorios sensibles durante 12 horas. Considerando estos resultados y la CIM 90 (≤ 0.06 μg/ml) frente a bacterias como Pasteurella haemolitica y P. multocida , se propone como tratamiento de este tipo de cuadros infecciosos en caprinos, una dosis de mantenimiento de 1.3 mg/kg cada 12 horas por via intramuscular, cuyo predictor de eficacia (t > CIM) se calculo en 77.8 %. Palabras clave: cabras, cefalosporinas, ceftiofur, farmacocinetica, Pasteurella spp . Summary Pharmacokinetic parameters of ceftiofur sodium were determined with a unique dose of 2.2 mg/kg either by the intravenous on the intramuscular routes, in a crossed design treatment in non pregnant adult female goats (n= 6). Variations in plasmatic concentrations over time were determined by the microbiological assay in Mueller-Hinton agar, with Providencia alcalifaciens as indicator. The limit of quantification was set in 0.039 mg/ml. The plasmatic concentrations of Ceftiofur were determined by the non compartimental pharmacokinetic model using sofware PK Solution 2.0. The parameters obtained when the intravenous route was used were: average elimination time (t 1/2 B ) = 1.63 ± 0.04 hours, total clearance (Cl tot ) = 3.3 ± 1.1 ml/kg/min, volume of distribution (Vd ss ) = 0.38 ± 0.19 L/Kg, area under the curve (ABC) = 716.5 ± 225.5 mg/min/ml. These values did not differ significantly from those obtained by the intramuscular test (P max ) of 3.6 ± 0.5 mg/ml was obtained at a maximum time (t max ) of 0.53 ± 0.31 min, and the bioavailability was high (97.6 ± 0.1%). The results indicate that the intramuscular application provides fast absorption and optimal bioavailability, generating plasmatic levels that exceed the MIC 90 for sensitive respiratory pathogens for a period of 12 hours. Considering these results and a MIC (≤ 0.06 mg/ml) for bacteria like Pasteurella haemolitica and P. multocida , the treatment of this type of infections in goats, requires 1.3 mg/Kg every 12 hours by intramuscular route, to obtain a predictive effectiveness (t > MIC) of 77.8%. Key words: ceftiofur, cephalosporins, goats, Pasteurella spp , pharmacokinetics.