In vivo Pharmacokinetic and Pharmacodynamic (PK/PD) Modeling and Establishment of the PK/PD Cutoff of Florfenicol Against Pasteurella multocida in Ducks

• Published in: Frontiers in microbiology Vol. 11; p. 616685
• Main Authors: Xiao, Xia, Lan, Weixuan, Zhao, Yaqin, Li, Ruichao, Liu, Yuan, Liu, Juan, Wang, Zhiqiang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 11.01.2021
• Subjects: dose; florfenicol; Microbiology; P. multocida; PK/PD cutoff; PK/PD modeling; PK/PD modeling; dose; P. multocida; florfenicol; PK/PD cutoff
• DOI: 10.3389/fmicb.2020.616685
• ISSN: 1664-302X

can invade and translocate through endothelial cells and result in vascular-system infection, which can cause severe economic losses in the poultry industry. Antibacterial therapy (especially florfenicol) plays an important part in controlling infection. To preserve the effect of florfenicol, pharmacokinetic/pharmacodynamic (PK/PD) modeling of florfenicol against three strains in duck was established. Then, the efficacy of the currently marketed dose, a rational dosage regimen for populations, and the PK/PD cutoff were predicted through Monte Carlo simulations (MCSs). The area under the concentration-time curve from 0 to 24 h/minimum inhibitory concentration (AUC /MIC) was the optimal PK/PD parameter. The PK/PD surrogate values of florfenicol against were similar using different organs as the PD target, but varied in different strains. For the florfenicol-sensitive strain 0825Y , when the AUC /MIC reached 117.54 and 108.19, florfenicol showed a bactericidal effect in the liver and lung, respectively. For the florfenicol-sensitive strain 0901J , the corresponding value was 78.39 and 54.30, respectively. For the florfenicol-resistant strain JY160110, florfenicol could attain a maximum effect of 1 - log reduction in bacteria in the liver and lung when the AUC /MIC reached 2.03 and 2.06, respectively. The PK/PD-based prediction for the population dose indicated a poor effect for the low end of the currently marketed dose (40 mg/kg body weight per day), but a robust effect for the high end of the currently marketed dose (60 mg/kg body weight per day) with a target attainment rate of 92.79% and 81.44% against in mainland China and worldwide, respectively. The recommended dose optimized by MCSs was 52 mg/kg body weight in mainland China. The PK/PD cutoff of florfenicol against at the low end and high end of the current daily dose (40 and 60 mg/kg body weight) and predicted daily dose in mainland China (52 mg/kg body weight) was 0.25, 4, and 0.5 μg/ml, respectively. These results suggested that more than one strain should be involved for PK/PD modeling and contributed to rational use of florfenicol in populations. We also provided fundamental data for determination of florfenicol breakpoints in poultry.