Comparison of PK/PD Targets and Cutoff Values for Danofloxacin Against Pasteurella multocida and Haemophilus parasuis in Piglets.
Comparison of PK/PD Targets and Cutoff Values for Danofloxacin Against Pasteurella multocida and Haemophilus parasuis in Piglets.
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达氧氟沙星对仔猪多杀性巴氏杆菌和副猪嗜血杆菌的 PK/PD 目标和临界值比较
DOI：
10.3389/fvets.2022.811967
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发表时间：
2022
影响因子：
3.2
通讯作者：
Liao XP
中科院分区：
文献类型：
--
作者：
Zhou YF;Sun Z;Wang RL;Li JG;Niu CY;Li XA;Feng YY;Sun J;Liu YH;Liao XP
达诺沙星是一种合成的具有广谱活性的氟喹诺酮类药物，用于兽药。本研究旨在评价丹诺沙星对仔猪体内多杀性巴氏杆菌和副猪嗜血杆菌的药代动力学/药效学(PK/PD)指标、PK/PD临界值和最佳剂量。测定了仔猪静脉注射和肌肉注射2.5 mg/kg后单次给药的血清药代动力学。肌注2.5 mg/kg后，达诺沙星吸收良好，生物利用度达95.2%。931株多杀性巴氏杆菌和263株副猪嗜血杆菌对达诺沙星的流行病学截止(ECOFF值)分别为0.03和4 mg/L。猪血清中测得的丹诺沙星最低抑菌浓度明显低于人工肉汤中测得的最低抑菌浓度，副猪嗜血杆菌的肉汤/血清比值为4.33。与多杀性巴氏杆菌相比，达诺沙星对副猪嗜血杆菌的抗生素后效应(3.18~6.60h)和抗生素后亚MIC效应(7.02~9.94h)均显著延长。多杀性巴氏杆菌血清中丹诺沙星浓度-时间曲线下面积/最低抑菌浓度(AUC24小时/MIC)靶点的平均面积(AUC24小时/MIC)分别为32和49.8，副猪霍乱杆菌分别为14.6和37.8。多杀性巴氏杆菌相同终点的丹诺沙星AUC 2 4h/MIC靶点高于副猪霍乱杆菌。通过蒙特卡罗模拟计算得出，在当前剂量为2.5 mg/kg时，丹诺沙星对多杀性巴氏杆菌和副猪嗜血杆菌的pK/pD截止值分别为0.125和0.5 mg/L。达诺沙星覆盖本研究中多杀性巴氏杆菌和副猪嗜血杆菌总体MIC种群分布的目标达标率(PTA)为90%的预测最佳剂量分别为2.38和13.36 mg/kg。这些基于PK/PD的结果对临床剂量优化和评估丹诺沙星治疗涉及这些病原体的猪呼吸道感染的敏感性断点具有潜在的相关性。
Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against P. multocida and H. parasuis in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.5 mg/kg. Danofloxacin was well absorbed and fully bioavailable (95.2%) after intramuscular administration of 2.5 mg/kg. The epidemiological cutoff (ECOFF) values of danofloxacin from 931 P. multocida isolates and 263 H. parasuis isolates were 0.03 and 4 mg/L, respectively. Danofloxacin MICs determined in porcine serum were markedly lower than those measured in artificial broth, with a broth/serum ratio of 4.33 for H. parasuis. Compared to P. multocida, danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against H. parasuis. The mean area under the concentration-time curve/MIC (AUC24h/MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for P. multocida, whereas they were 14.6 and 37.8, respectively, for H. parasuis. Danofloxacin AUC24h/MIC targets for the same endpoints for P. multocida were higher than those for H. parasuis. At the current dose of 2.5 mg/kg, the PK/PD cutoff (COPD) values of danofloxacin against P. multocida and H. parasuis were calculated to be 0.125 and 0.5 mg/L, respectively, based on Monte Carlo simulations. The predicted optimum doses of danofloxacin for a probability of target attainment (PTA) of > 90% to cover the overall MIC population distributions of P. multocida and H. parasuis in this study were 2.38 and 13.36 mg/kg, respectively. These PK/PD-based results have potential relevance for the clinical dose optimization and evaluation of susceptibility breakpoints for danofloxacin in the treatment of swine respiratory tract infections involving these pathogens.
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影响因子：
5.2
作者：
Toutain PL;Bousquet-Mélou A;Damborg P;Ferran AA;Mevius D;Pelligand L;Veldman KT;Lees P
通讯作者：
Lees P
影响因子：
2.6
作者：
Kim, Jongho;Kim, Jong Wan;Kim, Ha-Young
通讯作者：
Kim, Ha-Young
影响因子：
1.3
作者：
Lees, P.;Illambas, J.;Toutain, P. -L.
通讯作者：
Toutain, P. -L.
影响因子：
2.4
作者：
Lauritzen, B;Lykkesfeldt, J;Friis, C
通讯作者：
Friis, C
影响因子：
2.3
作者：
Tao, Meng-Ting;Zhou, Yu-Feng;Liao, Xiao-Ping
通讯作者：
Liao, Xiao-Ping