Yu Yang, Zhou Yu Feng, Sun Jian, Shi Wei, Liao Xiao Ping, Liu Ya Hong
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China.
BMC Vet Res. 2017 Feb 10;13(1):47. doi: 10.1186/s12917-017-0964-0.
This study focused on utilizing pharmacokinetics/pharmacodynamics (PK/PD) modeling to optimize therapeutic dosage regimens of sarafloxacin against avian pathogenic Escherichia. coli O78 strain in Muscovy ducks. The ex vivo PK/PD study of sarafloxacin was conducted in Muscovy ducks after intravenous (i.v.) and oral (p.o.) administrations at a single dose of 10 mg/kg bodyweight (BW). The serum samples were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC) using a fluorescence detection method. Sarafloxacin PK data were analyzed by a non-compartmental method using Winnonlin software.
Calculations of the area under the concentration-time curves (AUC) were 8.57 ± 0.59 and 8.37 ± 0.29 μg · h/ml following i.v. and p.o. administration, respectively. Elimination half-lives (t ) were 6.11 ± 0.99 h and 8.21 ± 0.64 h for i.v. injection and p.o. administration, respectively. The mean in vitro plasma protein binding of sarafloxacin was 39.3%. Integration using the sigmoid E model, the mean values of AUC/MIC needed for bacteriostatic, bactericidal and bacterial eradication action were 25.4, 40.6, and 94.4 h, respectively.
Sarafloxacin administered at a 10 mg/kg dose may be insufficient for treatment of E. coli O78 infections with an MIC equally to or over 0.125 μg/ml. Furthermore, higher doses of sarafloxacin are required to minimize antimicrobial resistance considering the MPC theory.
本研究聚焦于利用药代动力学/药效学（PK/PD）模型来优化针对番鸭源致病性大肠杆菌O78菌株的沙拉沙星治疗剂量方案。在番鸭静脉注射（i.v.）和口服（p.o.）单剂量10毫克/千克体重（BW）的沙拉沙星后，开展了其体外PK/PD研究。血清样本采用荧光检测法通过反相高效液相色谱（RP-HPLC）进行分析。沙拉沙星的PK数据使用Winnonlin软件通过非房室方法进行分析。
静脉注射和口服给药后，浓度-时间曲线下面积（AUC）的计算值分别为8.57±0.59和8.37±0.29微克·小时/毫升。静脉注射和口服给药的消除半衰期（t）分别为6.11±0.99小时和8.21±0.64小时。沙拉沙星的体外血浆蛋白平均结合率为39.3%。使用S型E模型进行整合，抑菌、杀菌和细菌清除作用所需的AUC/MIC平均值分别为25.4、40.6和94.4小时。
以10毫克/千克的剂量给药，沙拉沙星可能不足以治疗MIC等于或超过0.125微克/毫升的大肠杆菌O78感染。此外，考虑到MPC理论，需要更高剂量的沙拉沙星来最小化抗菌耐药性。
