Xia Xirui, Zhao Huifang, Li Yaxi, Long Xiangyang, Liu Xuezhen, Bai Mingyang, Tang Youzhi, Shen Xiangguang, Ding Huanzhong
Guangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, China.
Guangdong Key Laboratory for Veterinary Drug Development and Safety evaluation, College of Veterinary Medicine, South China Agricultural University, 510642 Guangzhou, China.
Poult Sci. 2025 May 4;104(8):105249. doi: 10.1016/j.psj.2025.105249.
Mycoplasma gallisepticum (M. gallisepticum, MG) is the primary pathogen of chronic respiratory disease (CRD) in chickens and leads to pneumonia and air sacculitis in infected chickens and a corresponding economic loss for the poultry industry. The pleuromutilins have excellent anti-mycoplasmal activity and we evaluated the in vivo activity of a new derivative 22-((4-((2-furan-1-yl)acetamido)phenyl)thio) deoxypleuromutilin (p-furoylamphenmulin) against M. gallisepticum. A plasma pharmacokinetic (PK) study and an in vivo pharmacodynamic (PD) study of p-furoylamphenmulin were performed using an M. gallisepticum-infected chicken model. Based on the PK/PD results, a preliminary recommended dose was calculated. The minimum inhibitory concentration (MIC) of p-furoylamphenmulin against M. gallisepticum was 0.001953125 μg/mL. PK results indicated that the absorption half-life (T) in infected chicks was 0.10 h, elimination half-life (T) was 4.23 h. The areas under the concentration-time curve at 24 h (AUC) for 5, 40, and 80 mg/kg single-dose injections were 1.49, 10.15, and 18.56 μg·h/mL, respectively. The peak concentrations (C) of 5, 40, and 80 mg/kg were 0.56, 5.79, and 9.53 μg/mL, respectively. The PD results indicated that at doses of 70 and 80 mg/kg, the mycoplasmal counts in lungs decreased by 3.39 and 3.28 LogCFU/mL, respectively, achieving a bactericidal effect. Through PK/PD fitting, the target values corresponding to reducing the lung mycoplasma load by 3 Log CFU/mL of AUC/MIC and C/MIC were 8288.29 h and 4299.30, respectively, and the calculated dosage using formula (2) was 62.64 mg/kg, under the regimen of intramuscular injection once every 24 h for 3 consecutive days. In addition, the effect of high-dose p-furoylamphenmulin on the relief of air sac lesions was significant. These results provide a basis for developing and applying p-furoylamphenmulin and provide a preliminary medication regimen.
鸡毒支原体（MG）是鸡慢性呼吸道疾病（CRD）的主要病原体，可导致感染鸡发生肺炎和气囊炎，给家禽业造成相应的经济损失。截短侧耳素类药物具有优异的抗支原体活性，我们评估了一种新衍生物22-((4-((2-呋喃-1-基)乙酰胺基)phenyl)硫代)脱氧截短侧耳素（对-呋喃甲酰安福霉素）对鸡毒支原体的体内活性。使用鸡毒支原体感染的鸡模型对p-呋喃甲酰安福霉素进行了血浆药代动力学（PK）研究和体内药效学（PD）研究。根据PK/PD结果计算出初步推荐剂量。p-呋喃甲酰安福霉素对鸡毒支原体的最低抑菌浓度（MIC）为0.001953125μg/mL。PK结果表明，感染雏鸡的吸收半衰期（T）为0.10小时，消除半衰期（T）为4.23小时。5、40和80mg/kg单剂量注射在24小时时的血药浓度-时间曲线下面积（AUC）分别为1.49、10.15和18.56μg·h/mL。5、40和80mg/kg的峰浓度（C）分别为0.56、5.79和9.53μg/mL。PD结果表明，在70和80mg/kg剂量下，肺内支原体计数分别下降3.39和3.28 LogCFU/mL，达到杀菌效果。通过PK/PD拟合，将肺支原体载量降低3 Log CFU/mL时对应的AUC/MIC和C/MIC的目标值分别为8288.29小时和4299.30，在每24小时肌肉注射一次、连续3天的给药方案下，使用公式（2）计算出的剂量为62.64mg/kg。此外，高剂量p-呋喃甲酰安福霉素对缓解气囊病变的效果显著。这些结果为p-呋喃甲酰安福霉素的研发和应用提供了依据，并提供了初步的用药方案。
