The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs  

作　　者：Yuanyuan Yuan Boyu An Shuyu Xie Wei Qu Haihong Hao Lingli Huang Wanhe Luo Jixiang Liang Dapeng Peng 

机构地区：[1]National Reference Laboratory of Veterinary Drug Residues(HZAU)and MOA Key Laboratory for the Detection of Veterinary Drug Residues in Foods,Huazhong Agricultural University,Wuhan,Hubei 430070,People's Republic of China [2]State Key Laboratory of Agricultural Microbiology,Huazhong Agricultural University,Wuhan,Hubei 430070,People's Republic of China [3]College of Veterinary Medicine,Huazhong Agricultural University,Wuhan 430070,Hubei,People's Republic of China [4]Shenzhen Institute of Nutrition and Health,Huazhong Agricultural University,Wuhan 430070,Hubei,People's Republic of China [5]Shenzhen Branch,Guangdong Laboratory for Lingnan Modern Agriculture,Genome Analysis Laboratory of the Ministry of Agriculture,Agricultural Genomics Institute at Shenzhen,Chinese Academy of Agricultural Sciences,Shenzhen,People's Republic of China

出　　处：《Animal Diseases》2023年第4期286-298,共13页动物疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(32072920);the National Key Research and Development Program of China(2017YFD0501402);the Fundamental Research Funds for the Central Universities(2662022DKPY007);the HZAU-AGIS Cooperation Fund(SZYJY2022024).

摘　　要：Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.

关 键 词：FLORFENICOL Doxycycline hydrochloride PK-PD PIG Dose regimen Actinobacillus pleuropneumoniae 

分 类 号：S85[农业科学—兽医学]