Pharmacokinetics and bioavailability of fosfomycin in broiler chicken

ALEJANDRO SORACI; PEREZ; MARTINEZ; DIEGUEZ, S.; TAPIA; COULSI; HARKES; ROMANO

REVUE DE MEDICINE VETERINAIRE

Ecole nationale vétérinaire de Toulouse

Año: 2011 vol. 162 p. 358 - 363

The pharmacokinetics and the bioavailability of fosfomycin salts (sodium fosfomycin and calcium fosfomycin) were studied in broiler chickens after intravenous, intramuscular and oral administration. Plasma concentrations were measured by high performance liquid ms/ms. After IV administration the area under the fosfomycin concentration: time curve in plasma was AUC(0-24) of 318 µg.h/ml and the volume of distribution (Vd) of 231 ml/kg. The elimination was rapid with a plasma clearance of 115 ml/kg/hr and a T1/2 of 1.4 h. Peak plasmatic concentration (Cmax), Tmax, AUC(0-24) and bioavailability for the oral administration (40 mg/kg) were 29.8 µg/ml, 2.0 h, 125 µg.h/ml and 39.3% respectively. Peak plasmatic concentration (Cmax), Tmax, AUC(0-24) and bioavailability for the IM administration (10 mg/kg) were 20.7 µg/ml, 0.8 h, 65.1 µg.h/ml and 82% respectively. Considering a minimum inhibitory concentration (MIC90) of 8 µg/ml for fosfomycin on E.coli in broilers, the ratios AUC0-24/CMI90 estimated for fosfomycin after oral and IM administrations were 15.6 and 8.1 respectively. This suggests an insufficient therapeutic efficacy in vivo when administered in a unique dose. For this reason, a loading dose of 40 mg/kg via drinking water has been recently proposed for disodium fosfomycin versus E. coli strains, followed by ad libitum administration of 40 mg/kg 8h later (i.e. 80 mg/kg per day).