PK-PD Integration Modeling and Cutoff Value of Florfenicol against in Pigs.

The aims of the present study were to establish optimal doses and provide an alternate CO for florfenicol against based on pharmacokinetic-pharmacodynamic integration modeling. The recommended dose (30 mg/kg b.w.) were administered in healthy pigs through intramuscular and intravenous routes for pharmacokinetic studies. The main pharmacokinetic parameters of , AUC, AUC, Ke, , MRT, and Cl, were estimated as 4.44 μg/ml, 88.85 μg⋅h/ml, 158.56 μg⋅h/ml, 0.048 h, 14.46 h, 26.11 h, 4 h and 0.185 L/h⋅kg, respectively. The bioavailability of florfenicol was calculated to be 99.14% after I.M administration. A total of 124 from most cities of China were isolated to determine the minimum inhibitory concentration (MIC) of florfenicol. The MIC and MIC were calculated as 1 and 2 μg/ml. A serotype 2 (WH-2), with MIC value similar to MIC, was selected as a representative for an and pharmacodynamics study. The MIC values of WH-2 in TSB and plasma were 2 μg/ml, and the MBC/MIC ratios were 2 in TSB and plasma. The MPC was detected to be 3.2 μg/ml. According to inhibitory sigmoid model, plasma AUC/MIC values of florfenicol versus were 37.89, 44.02, and 46.42 h for the bactericidal, bacteriostatic, and elimination activity, respectively. Monte Carlo simulations the optimal doses for bactericidal, bacteriostatic, and elimination effects were calculated as 16.5, 19.17, and 20.14 mg/kg b.w. for 50% target attainment rates (TAR), and 21.55, 25.02, and 26.85 mg/kg b.w. for 90% TAR, respectively. The PK-PD cutoff value (CO) analyzed from MCS for florfenicol against was 1 μg/ml which could provide a sensitivity cutoff value. These results contributed an optimized alternative to clinical veterinary medicine and showed that the dose of 25.02 mg/kg florfenicol for 24 h could have a bactericidal action against after I.M administration. However, it should be validated in clinical practice in the future investigations.