PHARMACOKINETIC/PHARMACODYNAMIC ANALYSIS OF A THERAPEUTIC REGIMEN OF MARBOFLOXACIN IN GOATS WITH MASTITIS BY MONTE CARLO SIMULATION

LORENZUTTI AUGUSTO MATÍAS; DE LUCAS BURNEO JOSÉ JULIO; SAN ANDRÉS MANUEL IGNACIO; ZARAZAGA MARÍA DEL PILAR; HIMELFARB MARTÍN ALEJANDRO; LITTERIO NICOLÁS JAVIER

Mar del Plata

Congreso; XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL; 2016

Sociedad Argentina de Farmacología Experimental

Goat mastitis generates economic losses and threatens public health. Coagulase-negative staphylococci (CNS) and S. aureus are principal pathogens. Marbofloxacin (MFX) is a fluoroquinolone approved for veterinary use indicated for mastitis. The objectives of this study were to evaluate the pharmacokinetics and milk bioavailability of MFX by IM route in lactating goats, determine MIC and MPC from regional pathogens, make a PK/PD analysis by Monte Carlo simulation, and correlate the PK/PD results with clinical response and milk culture. Seven goats with mastitis by CNS were included. MFX was administered by IM route at 10mg/kg/24hx5days. Milk production, pH and culture were performed once a day. Serum and milk samples were quantified by microbiological method, and a non-compartmental model was used. Milk bioavailability of MFX was evaluated by AUC24milk/serum ratio. MICs and MPCs were obtained from regional strains of CNS (n=106) and S. aureus (n=8) isolated from caprine mastitis in Córdoba, Argentina. 10000-subjects Monte Carlo simulation was carried out. PK/PD endpoints were AUC/MIC>40, 50 and 60, Cmax/MIC>10, AUC/MPC>13.5 and Cmax/MPC>1.2. Probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated. AUC24milk/serum ratios were >1. During treatment, milk production increased and pH decreased in infected udders, consistent with lower values of AUC in serum and milk. No pharmacokinetic differences in milk between healthy and infected udders were observed. All animals completed the study with negative cultures. The proposed dose regimen of MFX presented a PTA>90% only for MICs of 0.2-0.4µg/ml, but CFR was >90% for all endpoints. For AUC/MPC endpoint a PTA>90% were achieved only for MPCs of 0.8-1.6µg/ml. CFR was 90% was observed with MPCs of 0.8-3.2µg/ml, with a CFR