Yang Qingwen, Liu Xuesong, Zhang Chenghuan, Yong Kang, Clifton Alancia Carol, Ding Huanzhong, Liu Yun
Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Laboratory of Veterinary Pharmacology, Department of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing, China.
Front Pharmacol. 2019 Sep 24;10:1090. doi: 10.3389/fphar.2019.01090. eCollection 2019.
Gamithromycin is approved for the treatment and prevention of bovine respiratory disease (BRD), which is caused mainly by , and species. In this study, multiple dosage regimens were administered to the neutropenic mouse lung infection model in order to investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of gamithromycin treatment of and to further define the PK/PD parameter that best correlates with the efficacy of gamithromycin against . The PK characteristics of gamithromycin were analyzed after a single subcutaneous (s.c.) injection (1, 3, 6, and 9 mg/kg). The concentration-time profiles of unbound () gamithromycin in plasma samples were analyzed by non-compartmental analysis. The main PK parameters of gamithromycin for the area under the concentration-time curve from 0 to 24 h ( AUC) and the peak drug concentration ( ) values ranged from 0.86 to 8.42 µg·h/ml and from 0.55 to 5.69 µg/ml, respectively. The PD values were calculated based on multiple s.c. injections over 24 h (1, 3, 6, and 9 mg/kg at 6, 8, 12, and 24 h, respectively; total dosage 1-36 mg/ kg). The minimum inhibitory concentration (MIC) of gamithromycin against in mice serum was 0.15 μg/ml. Analysis of PK/PD indices using the inhibitory effect model indicated a strong correlation ( = 0.9624) between the AUC/MIC ratio and various antibacterial effects. The area under the unbound concentration-time curve over 24 h to MIC ( AUC/MIC) predicted for bacteriostatic action, 1-log reduction, 2-log reduction, and 3-log reduction were 56.77, 90.18, 143.06, and 239.44 h, respectively. These data may facilitate gamithromycin dosage optimization against in veterinary medicine.
加米霉素被批准用于治疗和预防主要由 、 和 种属引起的牛呼吸道疾病（BRD）。在本研究中，对中性粒细胞减少的小鼠肺部感染模型给予多种给药方案，以研究加米霉素治疗 的药代动力学/药效学（PK/PD）参数，并进一步确定与加米霉素抗 疗效最相关的PK/PD参数。单次皮下（s.c.）注射（1、3、6和9mg/kg）后分析加米霉素的PK特征。通过非房室分析血浆样品中游离（ ）加米霉素的浓度-时间曲线。加米霉素在0至24小时浓度-时间曲线下面积（AUC）和药物峰浓度（ ）值的主要PK参数分别为0.86至8.42μg·h/ml和0.55至5.69μg/ml。基于24小时内多次皮下注射（分别在6、8、12和24小时注射1、3、6和9mg/kg；总剂量1-36mg/ kg）计算PD值。加米霉素对小鼠血清中 的最低抑菌浓度（MIC）为0.15μg/ml。使用抑制效应 模型分析PK/PD指数表明，AUC/MIC比值与各种抗菌效应之间存在强相关性（ = 0.9624）。24小时游离浓度-时间曲线下面积与MIC之比（AUC/MIC）预测抑菌作用、1对数减少、2对数减少和3对数减少分别为56.77、90.18、143.06和239.44小时。这些数据可能有助于优化加米霉素在兽医学中抗 的给药剂量。
