摘要
为了制订达氟沙星对猪胸膜肺炎放线杆菌(Actinobacillus pleuropneumoniae,APP)的野生型临界值与在猪体内的药效学临界值,试验采用微量肉汤稀释法测定达氟沙星对115株APP的最小抑菌浓度(minimal inhibitory concentration,MIC),制订野生型临界值;选取5株MIC_(90)附近菌株进行毒力试验,测定达氟沙星对毒力最强的菌株的体外和半体内MIC及最小杀菌浓度(MBC),进行体外与间接体内杀菌试验;将18头猪随机分成健康组和患病组(按体重滴鼻接种APP 1×10^(9) cfu/kg),均按体重肌肉注射甲磺酸达氟沙星注射液2.5 mg/kg(以达氟沙星计),分别于给药后0.25,0.5,0.75,1,2,4,6,8,10,24,36小时时采集血液,采用高效液相色谱法测定血浆中的药物浓度;构建PK-PD模型,制订药效学临界值。结果表明:达氟沙星对APP的MIC分布范围为0.004~1μg/mL,制订的野生型临界值为0.5μg/mL;S3菌株的毒力最强;达氟沙星对S3菌株的体外和半体内MIC均为0.125μg/mL,MBC分别为0.125μg/mL和0.250μg/mL,抗菌作用为浓度依赖型。药动学参数:健康组达峰时间(T_(max))为(0.889±0.148)h,达峰浓度(C_(max))为(0.529±0.309)μg/mL,半衰期(T_(1/2))为(12.111±0.162)h,药时曲线下面积(AUC)为(5.016±0.404)μg/mL·h;患病组T_(max)为(0.833±0.150)h,C_(max)为(0.603±0.107)μg/mL,T_(1/2)为(8.567±0.178)h,AUC为(5.195±0.128)μg/mL·h,达氟沙星在患病猪体内吸收和消除较为迅速。达到抑菌、杀菌、清除效果的PK-PD值分别为8.823,11.950,14.810,预防、治疗、根治剂量分别为按体重2.170,2.940,3.643 mg/kg;达氟沙星对APP的药效学临界值为0.25μg/mL。说明达氟沙星体外对APP的野生型临界值为0.5μg/mL,体内药效学临界值为0.25μg/mL。
In order to develop the wild-type cut-off value and pharmacodynamic cut-off value in pigs of danofloxacin against Actinobacillus pleuropneumoniae(APP),in the experiment,the minimal inhibitory concentration(MIC)of danofloxacin against 115 isolates of Actinobacillus pleuropneumoniae was determined by the micro-broth dilution method,and the wild-type cut-off value was established.5 strains near MIC_(90) were selected for virulence test;the in vitro and semi-in vivo MIC and minimum bactericidal concentration(MBC)of danofloxacin to the most virulent strains were determined and in vitro and ex vivo bactericidal tests were conducted.18 pigs were randomly divided into healthy group and diseased group(APP 1×10^(9) cfu/kg by intranasal inoculation according to body weight),all of which were given 2.5 mg of danofloxacin mesylate injection intramuscularly per kilogram of body weight.Blood was collected at 0.25,0.5,0.75,1,2,4,6,8,10,24,and 36 h after ad⁃ministration,and the drug concentration in plasma was determined by high performance liquid chromatography.A PK-PD model was constructed to formulate the pharmacodynamic cut-off value.The results showed that the MIC of danofloxacin against Actinobacillus pleuropneumoniae was 0.004-1μg/mL,and the established wild-type cut-off value was 0.5μg/mL.The virulence of S3 strain was the strongest;the in vitro and semi-in vivo MIC of danofloxacin against S3 strain was both 0.125μg/mL,and the MBC was 0.125μg/mL and 0.250μg/mL,respectively.The antibacterial effect was concentration-dependent.Pharmacokinetic parameters:the time to peak(T_(max))in the healthy group was(0.889±0.148)h;the peak concentration(C_(max))was(0.529±0.309)μg/mL;the half-life(T_(1/2))was(12.111±0.162)h;the area under the curve(AUC)was(5.016±0.404)μg/mL·h.In the diseased group,T_(max) was(0.833±00.150)h;C_(max) was(0.603±0.107)μg/mL;T_(1/2) was(8.567±0.178)h;AUC was(5.195±0.128)μg/mL·h.The results indicated that danofloxacin was absorbed and eliminated rapid⁃ly in the sick pigs.The PK-PD values
作者
马飞洋
李泽坤
王申森
杨方
邹明
唐兆新
王鹤佳
徐士新
MA Feiyang;LI Zekun;WANG Shensen;YANG Fang;ZOU Ming;TANG Zhaoxin;WANG Hejia;XU Shixin(College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;College of Veterinary Medicine,Qingdao Agricultural University,Qingdao 266109,China;China Institute of Veterinary Drugs Control,Beijing 100001,China)
出处
《黑龙江畜牧兽医》
CAS
北大核心
2022年第19期112-120,共9页
Heilongjiang Animal Science And veterinary Medicine
基金
国家重点研发计划专项“畜禽重要病原耐药性检测与控制技术研究”(2016YFD0501302)。
关键词
达氟沙星
猪
胸膜肺炎放线杆菌
野生型临界值
药效学临界值
danofloxacin
porcine
Actinobacillus pleuropneumoniae
wild-type cut-off value
pharmacodynamic cut-off value
