Comparative pharmacokinetics of danofloxacin in healthy and Pasteurella multocida infected ducks
Comparative pharmacokinetics of danofloxacin in healthy and Pasteurella multocida infected ducks
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达氟沙星在健康鸭和多杀性巴氏杆菌感染鸭体内的药代动力学比较
DOI：
10.1111/jvp.12712
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发表时间：
2018-12-01
影响因子：
1.3
通讯作者：
Wang, Zhiqiang
中科院分区：
文献类型：
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作者：
Xiao, Xia;Lan, Weixuan;Wang, Zhiqiang
巴斯德菌multocida (P。多杀菌感染给养鸭业造成了巨大的经济损失。达诺沙星是一种仅用于动物的氟喹诺酮类药物，对stp具有良好的抗菌活性。multocida。本研究对丹诺沙星抗stp的体外药效学进行了研究。multocidawas研究。研究了丹诺沙星在健康人和p人血清和肺组织中的药动学。经单次口服5mg /kg体重（体重）后感染多病鸭。盐酸丹诺沙星抗stp。多杀力（C48‐1）分别为0.25、1和3.2 μg/ml。正常鸭在2.03 h时达到最大值0.34 μg/ml，病鸭在2.87 h时达到最大值0.35 μg/ml。与健康鸭的血清药动学比较，丹诺沙星在健康鸭和患病鸭体内的吸收率和吸收率基本一致。相比之下，清除速度较慢，健康动物和感染动物的消除半衰期（T1/2β）分别为13.17和16.18小时；两组的aus分别为5.70和7.68 μg hr/ml，说明感染鸭体内循环中的药物总量增加。正常动物与感染动物肺组织中最大浓度差异无统计学意义（8.96 vs 8.93 μg）。然而，tmaxin健康鸭比感染鸭的时间更长（4小时比1.75小时），这意味着danoflo沙星在健康鸭中的分布速度较慢。肺组织中danoflo沙星浓度约为血清浓度的24倍。在血清药代动力学分析中，健康鸭的theƒAUC0‐24 hr/ mic0为18.19，p为25.04。临床推荐剂量远低于氟喹诺酮类药物的pk / pd目标（125小时）。对于感染p的鸭子，5毫克/公斤体重的丹诺沙星剂量似乎是不够的。多杀，剂量为0.25 μg/ml。
Pasteurella multocida(P. multocida) infection causes substantial economic loss in the duck industry. Danofloxacin, a fluoroquinolone solely used in animals, shows good antibacterial activity againstP. multocida. In this study, the in vitro pharmacodynamics of danofloxacin againstP. multocidawas studied. The serum and lung tissue pharmacokinetics of danofloxacin were studied in healthy andP. multocidainfected ducks following oral administration of a single dose of 5 mg/kg body weight (b.w.). TheMIC,MBCandMPCof danofloxacin againstP. multocida(C48‐1) were 0.25, 1 and 3.2 μg/ml, respectively. TheCmax was 0.34 μg/ml, attained at 2.03 hr in healthy ducks, and was 0.35 μg/ml, attained at 2.87 hr in diseased ducks. Compared to the serum pharmacokinetics of danofloxacin in healthy ducks, the absorption rate and extent were similar in healthy and diseased animals. In contrast, the elimination rate was slower, with an elimination half‐life (T1/2β) of 13.17 and 16.18 hr for healthy and infected animals, respectively; theAUCs in the two groups were 5.70 and 7.68 μg hr/ml, respectively, which means the total amount of drug in the circulation was increased in the infected ducks. The maximum concentration in lung tissues between healthy and infected animals was not significantly different (8.96 vs. 8.93 μg/g). However, theTmaxin healthy ducks was longer than that in infected ducks (4 hr vs. 1.75 hr), which means that the distribution rate of danofloxacin was slower in healthy ducks. The concentration of danofloxacin in lung tissues was approximately 24‐fold higher than that in the serum. In the serum pharmacokinetic profiles, theƒAUC0‐24 hr/MICwas 18.19 in healthy ducks and was 25.04 inP. multocidainfected ducks at the clinical recommended dose, which is far from thePK/PDtarget (125 hr) of fluoroquinolones. Danofloxacin, at a dose of 5 mg/kg b.w., seems to be insufficient for ducks infected withP. multocida, with anMICequal to 0.25 μg/ml.