In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks
Riemerella anatipestifer causes serious infections, characterized by septicemia and serositis, in ducks and geese. R. anatipestifer is mainly controlled through antimicrobial chemotherapy. This study investigated the pharmacokinetic/pharmacodynamic (PK/PD) integration of florfenicol (FF) against R....
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Elsevier
2025-01-01
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| Series: | Poultry Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579124012136 |
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| author | Hui-Lin Zhang Fa-Lei Li Hui-Yang Chen Ding-Mei Qin Shu-Jun Sun Meng-Meng Zhang Huan-Zhong Ding Yong Liu |
| author_facet | Hui-Lin Zhang Fa-Lei Li Hui-Yang Chen Ding-Mei Qin Shu-Jun Sun Meng-Meng Zhang Huan-Zhong Ding Yong Liu |
| author_sort | Hui-Lin Zhang |
| collection | DOAJ |
| description | Riemerella anatipestifer causes serious infections, characterized by septicemia and serositis, in ducks and geese. R. anatipestifer is mainly controlled through antimicrobial chemotherapy. This study investigated the pharmacokinetic/pharmacodynamic (PK/PD) integration of florfenicol (FF) against R. anatipestifer by establishing a systemic infection model in ducks. For PK studies, FF was administrated intramuscularly (i.m.) at single doses of 2.5, 10, 20, and 40 mg/kg body weight. The concentrations of FF in blood, lung, and liver were determined. FF was rapidly eliminated in R. anatipestifer-infected ducks with T1/2kel values of 1.67, 2.2, and 1.62 h in the plasma, lung, and liver, respectively. For PD analysis, the infected ducks were administered FF via the i.m. route at doses of 5–80 mg/kg body weight, using 2 dosing regimens involving the administration of FF either once or twice over 24 h. The bacteria were counted 24 h after drug administration. Bactericidal effects in tissues (including those of the heart, liver, spleen, lung, kidney, and brain) were achieved at doses of ≥20 mg/kg following 2 i.m. injections of FF within 24 h. The data obtained were fitted to a sigmoidal Emax model. The results demonstrated that AUC24h/minimum inhibitory concentration (MIC) (R2 = 0.930) and Cmax/MIC (R2 = 0.930) were the optimal PK/PD parameters for describing the antibacterial activity of FF. The magnitudes of AUC24h/MIC and Cmax/MIC required to produce a drop of 3 Log10CFU/mL in the bacterial count were 58.56 h and 15.10, respectively. The MIC distribution of 164 R. anatipestifer strains for FF ranged from 0.25 to 16 μg/mL. Both the values of COWT derived from the ECOFFinder program and the COPD based on a 10,000-subject Monte Carlo simulation of FF against R. anatipestifer were 1 μg/mL, confirming that infections caused by strains with MIC ≤ 1 μg/mL could be effectively treated. Our study results may prove useful in optimizing FF regimens to treat R. anatipestifer infections. |
| format | Article |
| id | doaj-art-a7641ac17cbe43bfba36e227d0be6152 |
| institution | Kabale University |
| issn | 0032-5791 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Poultry Science |
| spelling | doaj-art-a7641ac17cbe43bfba36e227d0be61522025-01-22T05:40:47ZengElsevierPoultry Science0032-57912025-01-011041104635In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducksHui-Lin Zhang0Fa-Lei Li1Hui-Yang Chen2Ding-Mei Qin3Shu-Jun Sun4Meng-Meng Zhang5Huan-Zhong Ding6Yong Liu7School of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR ChinaSchool of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR ChinaSchool of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR ChinaSchool of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR ChinaSchool of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR ChinaSchool of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR ChinaGuangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR ChinaSchool of Biological and Food Engineering, Fuyang Normal University, Fuyang 236037, PR China; Corresponding author: School of Biological and Food Engineering, Fuyang Normal University, Fuyang, 236037, China.Riemerella anatipestifer causes serious infections, characterized by septicemia and serositis, in ducks and geese. R. anatipestifer is mainly controlled through antimicrobial chemotherapy. This study investigated the pharmacokinetic/pharmacodynamic (PK/PD) integration of florfenicol (FF) against R. anatipestifer by establishing a systemic infection model in ducks. For PK studies, FF was administrated intramuscularly (i.m.) at single doses of 2.5, 10, 20, and 40 mg/kg body weight. The concentrations of FF in blood, lung, and liver were determined. FF was rapidly eliminated in R. anatipestifer-infected ducks with T1/2kel values of 1.67, 2.2, and 1.62 h in the plasma, lung, and liver, respectively. For PD analysis, the infected ducks were administered FF via the i.m. route at doses of 5–80 mg/kg body weight, using 2 dosing regimens involving the administration of FF either once or twice over 24 h. The bacteria were counted 24 h after drug administration. Bactericidal effects in tissues (including those of the heart, liver, spleen, lung, kidney, and brain) were achieved at doses of ≥20 mg/kg following 2 i.m. injections of FF within 24 h. The data obtained were fitted to a sigmoidal Emax model. The results demonstrated that AUC24h/minimum inhibitory concentration (MIC) (R2 = 0.930) and Cmax/MIC (R2 = 0.930) were the optimal PK/PD parameters for describing the antibacterial activity of FF. The magnitudes of AUC24h/MIC and Cmax/MIC required to produce a drop of 3 Log10CFU/mL in the bacterial count were 58.56 h and 15.10, respectively. The MIC distribution of 164 R. anatipestifer strains for FF ranged from 0.25 to 16 μg/mL. Both the values of COWT derived from the ECOFFinder program and the COPD based on a 10,000-subject Monte Carlo simulation of FF against R. anatipestifer were 1 μg/mL, confirming that infections caused by strains with MIC ≤ 1 μg/mL could be effectively treated. Our study results may prove useful in optimizing FF regimens to treat R. anatipestifer infections.http://www.sciencedirect.com/science/article/pii/S0032579124012136Riemerella anatipestiferFlorfenicolPK/PD modelin vivoPK/PD cutoff |
| spellingShingle | Hui-Lin Zhang Fa-Lei Li Hui-Yang Chen Ding-Mei Qin Shu-Jun Sun Meng-Meng Zhang Huan-Zhong Ding Yong Liu In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks Poultry Science Riemerella anatipestifer Florfenicol PK/PD model in vivo PK/PD cutoff |
| title | In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks |
| title_full | In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks |
| title_fullStr | In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks |
| title_full_unstemmed | In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks |
| title_short | In vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against Riemerella anatipestifer in ducks |
| title_sort | in vivo pharmacokinetic and pharmacodynamic study and cutoff of florfenicol against riemerella anatipestifer in ducks |
| topic | Riemerella anatipestifer Florfenicol PK/PD model in vivo PK/PD cutoff |
| url | http://www.sciencedirect.com/science/article/pii/S0032579124012136 |
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