Zhang Huilin, Mao Chunxiao, Li Jinju, Huang Zilong, Gu Xiaoyan, Shen Xiangguang, Ding Huanzhong
Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.
Front Pharmacol. 2019 Sep 20;10:1088. doi: 10.3389/fphar.2019.01088. eCollection 2019.
Doxycycline is a broad-spectrum antibacterial drug. It is used widely to treat diseases caused by species. We investigated the antibacterial activity of doxycycline against the strain ATCC25934. The minimum inhibitory concentration (MIC) of doxycycline against determined by a microdilution method was 0.125 μg/ml. Static time-kill curves with constant drug concentrations (0-64 MIC) showed that a bacteriostatic effect occurred if the doxycycline concentration reached 4 MIC. Doxycycline produced a maximum antimycoplasmal effect (reduction of 2.76 logCFU/ml) at 64 MIC within 48 h. The effect of doxycycline against was analyzed by a sigmoid model, and there was high correlation between the kill rate and doxycycline concentration ( = 0.986). A one-compartment open model with first-order absorption was adopted and was used to simulate doxycycline pharmacokinetics in porcine plasma. The dynamic time-concentration curve showed that the area under the curve at 24 h (AUC) and (peak concentration) after each drug administration was 1.78-48.4 μg h/ml and 0.16-3.41 μg/ml, respectively. The reduction of (logCFU/ml) for 1, 2.5, 5, 7.5, 10, 15, 20, and 30 mg/kg body weight was 0.16, 1.29, 1.75, 2.94, 3.35, 3.91, 4.35, and 5.77, respectively, during the entire experiment, respectively. When the dose was >10 mg/kg body weight, continuous administration for 3 days could achieve a bactericidal effect. The correlation coefficient of AUC/MIC, /MIC, and %T > MIC (the cumulative percentage of time over a 24-h period that the drug concentration exceeds the MIC) with antibacterial effect was 0.917, 0.923, and 0.823, respectively. Doxycycline showed concentration-dependent activity, and the value of AUC/MIC and /MIC required to produce a drop of 1 logCFU/ml was 164 h and 9.89, respectively.
强力霉素是一种广谱抗菌药物。它被广泛用于治疗由多种细菌引起的疾病。我们研究了强力霉素对菌株ATCC25934的抗菌活性。通过微量稀释法测定，强力霉素对该菌株的最低抑菌浓度（MIC）为0.125μg/ml。在恒定药物浓度（0 - 64倍MIC）下的静态时间杀菌曲线表明，当强力霉素浓度达到4倍MIC时会产生抑菌作用。在48小时内，强力霉素在64倍MIC时产生最大抗支原体效果（降低2.76 logCFU/ml）。通过S形Emax模型分析了强力霉素对该菌株的作用，杀灭率与强力霉素浓度之间存在高度相关性（r = 0.986）。采用具有一级吸收的单室开放模型来模拟强力霉素在猪血浆中的药代动力学。动态时间 - 浓度曲线表明，每次给药后24小时的曲线下面积（AUC）和Cmax（峰值浓度）分别为1.78 - 48.4μg·h/ml和0.16 - 3.41μg/ml。在整个实验过程中，体重1、2.5、5、7.5、10、15、20和30mg/kg时，细菌数量减少（logCFU/ml）分别为0.16、1.29、1.75、2.94、3.35、3.91、4.35和5.77。当剂量>10mg/kg体重时，连续给药3天可达到杀菌效果。AUC/MIC、Cmax/MIC和%T > MIC（药物浓度超过MIC的24小时累积时间百分比）与抗菌效果的相关系数分别为0.917、0.923和0.823。强力霉素表现出浓度依赖性活性，使细菌数量下降1 logCFU/ml所需的AUC/MIC和Cmax/MIC值分别为164小时和9.89。
