Huang Anxiong, Mao Feng, Huang Lingli, Xie Shuyu, Pan Yuanhu, Qu Wei, Cheng Guyue, Liu Zhenli, Yuan Zonghui, Peng Dapeng, Hao Haihong
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for Detection of Veterinary Drug Residues, Wuhan 430070, China.
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan 430070, China.
Antibiotics (Basel). 2022 Feb 21;11(2):283. doi: 10.3390/antibiotics11020283.
() causes severe respiratory diseases in pigs and is also an important pathogen causing hidden dangers to public health and safety. Acetylkitasamycin is a new macrolide agent that has shown good activity to Gram-positive cocci such as The purpose of this study was to perform pharmacokinetic-pharmacodynamic (PK-PD) modeling to formulate a dosing regimen of acetylkitasamycin for treatment of and to decrease the emergence of acetylkitasamycin-resistant . The minimal inhibitory concentration (MIC) of 110 isolates was determined by broth micro dilution method. The MIC of the 55 sensitive isolates was 1.21 μg/mL. The strain HB1607 with MIC close to MIC and high pathogenicity was used for the PK-PD experiments. The MIC and MBC of HB1607 in both MH broth and pulmonary epithelial lining fluid (PELF) was 1 and 2 μg/mL, respectively. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to determine the concentration change of acetylkitasamycin in piglet plasma and PELF after intragastric administration of a single dose of 50 mg/kg b.w. acetylkitasamycin. The PK parameters were calculated by WinNolin software. The PK data showed that the maximum concentration (C), peak time (T), and area under the concentration-time curve (AUC) were 9.84 ± 0.39 μg/mL, 4.27 ± 0.19 h and 248.58 ± 21.17 h·μg/mL, respectively. Integration of the in vivo PK data and ex vivo PD data, an inhibition sigmoid E equation was established. The dosing regimen of acetylkitasamycin for the treatment infection established as 33.12 mg/kg b.w. every 12 h for 3 days. This study provided a reasonable dosing regimen for a new drug used in clinical treatment, which can effectively be used to treat infection and slow down the generation of drug resistance.
（）可导致猪的严重呼吸道疾病，也是对公众健康和安全构成隐患的重要病原体。乙酰吉他霉素是一种新型大环内酯类药物，对革兰氏阳性球菌如具有良好活性。本研究的目的是进行药代动力学-药效学（PK-PD）建模，以制定乙酰吉他霉素治疗的给药方案，并减少耐乙酰吉他霉素菌株的出现。采用肉汤微量稀释法测定110株菌株的最低抑菌浓度（MIC）。55株敏感菌株的MIC为1.21μg/mL。将MIC接近MIC且致病性高的HB1607菌株用于PK-PD实验。HB1607在MH肉汤和肺上皮衬液（PELF）中的MIC和MBC分别为1和2μg/mL。采用液相色谱-串联质谱（LC-MS/MS）法测定仔猪单次灌胃50mg/kg体重乙酰吉他霉素后血浆和PELF中乙酰吉他霉素的浓度变化。通过WinNolin软件计算PK参数。PK数据显示，最大浓度（C）、达峰时间（T）和浓度-时间曲线下面积（AUC）分别为9.84±0.39μg/mL、4.27±0.19h和248.58±21.17h·μg/mL。整合体内PK数据和体外PD数据，建立了抑制S型E方程。确定治疗感染的乙酰吉他霉素给药方案为每12小时33.12mg/kg体重，共3天。本研究为临床治疗新药提供了合理的给药方案，可有效用于治疗感染并减缓耐药性的产生。
