Huang Lingli, Zhang Haiyang, Li Mei, Ahmad Ijaz, Wang Yulian, Yuan Zonghui
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, Hubei, China.
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Wuhan, Hubei, China.
BMC Vet Res. 2018 Oct 24;14(1):319. doi: 10.1186/s12917-018-1645-3.
The aim of this study was to optimize the dosage regimen of tylosin against S.suis in Pigs using pharmacokinetic-pharmacodynamic (PK-PD) modeling. The antibacterial activity of tylosin against S.suis CVCC606 was investigated in Mueller Hinton (MH) broth and serum. The objectives of this investigation were to study the PD data of tylosin against S.suis CVCC606 and the PK data of tylosin in healthy and diseased model of pigs and formulate a rational dosage regimen for the treatment of pig streptococcosis.
The minimum inhibitory concentrations (MIC) were 0.25 μg/mL, and the minimal bactericidal concentrations (MBC) were 1 μg/mL in MH broth and serum. The killing curve showed time-dependent activity and weak concentration-dependent antibacterial activity. A pig pneumoniae model of S. suis infection was built by inoculating subcutaneously with S. suis CVCC606. Tylosin was (10 mg/kg b.w) administered intramuscularly (IM) to the healthy and S.suis infected pigs, The pharmacokinetic properties, including area under the curve(AUC), peak concentration (C) and time to reach C (T), were determined in plasma using UV-HPLC method. The AUC, C and T in plasma of healthy and infected pigs were 10.80 ± 2.20 and 10.30 ± 3.46 μg.h/mL, 2.06 ± 0.43 and 2.37 ± 0.38 μg/mL, 1.95 ± 0.22 and 1.58 ± 0.49 h, respectively.
The in vivo PK and in vitro PD data were integrated to determine the surrogate marker of antibacterial activity, C/MIC, AUC/MIC and Twere 8.90, 43.21, 8.86 for healthy pigs, and 9.76, 41.18, 7.56 for infected pigs, respectively. Ex vivo AUC/MIC data were integrated with ex vivo bacterial count to calculate the values for bacteriostatic and bactericidal action, which were 10.67 h and 49.66 h for healthy pigs, 11.73 h and 43.03 h for pigs infected with S.suis. A dosage regimen of 5.32-19.50 mg/kg b.w. every 24 h should be sufficient for tylosin against S.suis.
本研究的目的是使用药代动力学 - 药效学（PK - PD）模型优化泰乐菌素对猪链球菌病的给药方案。在 Mueller Hinton（MH）肉汤和血清中研究了泰乐菌素对猪链球菌CVCC606的抗菌活性。本研究的目的是研究泰乐菌素对猪链球菌CVCC606的药效学数据以及泰乐菌素在健康猪和患病猪模型中的药代动力学数据，并制定合理的给药方案用于治疗猪链球菌病。
在MH肉汤和血清中，最小抑菌浓度（MIC）为0.25μg/mL，最小杀菌浓度（MBC）为1μg/mL。杀菌曲线显示出时间依赖性活性和较弱的浓度依赖性抗菌活性。通过皮下接种猪链球菌CVCC606建立了猪链球菌感染的肺炎模型。对健康猪和感染猪链球菌的猪肌肉注射（IM）泰乐菌素（10mg/kg体重）。使用紫外 - 高效液相色谱法测定血浆中的药代动力学特性，包括曲线下面积（AUC）、峰浓度（C）和达到C的时间（T）。健康猪和感染猪血浆中的AUC、C和T分别为10.80±2.20和10.30±3.46μg·h/mL、2.06±0.43和2.37±0.38μg/mL、1.95±0.22和1.58±0.49h。
整合体内PK和体外PD数据以确定抗菌活性的替代指标，健康猪的C/MIC、AUC/MIC和T分别为8.90、43.21、8.86，感染猪分别为9.76、41.18、7.56。将体外AUC/MIC数据与体外细菌计数相结合，计算抑菌和杀菌作用的值，健康猪分别为10.67h和49.66h，感染猪链球菌的猪分别为11.73h和43.03h。每24小时5.32 - 19.50mg/kg体重的给药方案对泰乐菌素对抗猪链球菌应该足够。
