Qu Wei, Dong Mengxiao, Pan Yuanhu, Xie Shuyu, Yuan Zonghui, Huang Lingli
National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan 430070, China.
MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China.
Pharmaceutics. 2022 Mar 28;14(4):730. doi: 10.3390/pharmaceutics14040730.
In order to effectively treat the infection of and reduce the emergence of drug-resistant bacteria, an aditoprim (ADP) injection was developed in this study. The pharmaceutical property investigation results demonstrated that ADP injection was a clear yellow liquid with 10 g ADP distributing in every 100 mL solution uniformly. Its pH value and drug content were around 6.20 and 99.35100.40%, respectively. And quality assessment preliminarily indicated its reliable quality and stability. Additionally, the bronchoalveolar lavage fluid method was first applied to evaluate accurate ADP concentration at infection site in this study. Through pharmacodynamic assay, the MIC, MBC and MPC of ADP against CVCC 607 was 2 μg/mL, 4 μg/mL and 12.8 μg/mL, respectively. The bacteria growth inhibition curves showed that ADP was a concentration-dependent antibacterial drug, and the PK-PD model parameter of AUC/MIC was selected. The pharmacokinetic parameters of alveolar fluid evaluated by WinNonlin software revealed similar pharmacokinetic process of ADP in healthy pigs and infected pigs. Combined with pharmacokinetics-pharmacodynamics (PK-PD) modeling, the dosage regimen of 35 days with an interval of 12 h at 4.10 mg/kg or 5.91 mg/kg could be adopted to treat the infection of . Consequently, this ADP injection with a multi-dose protocol would be a promising antimicrobial product for efficient treatment of infection of pigs.
为有效治疗[感染类型]感染并减少耐药菌的出现,本研究开发了一种阿地普明(ADP)注射液。药物性质研究结果表明,ADP注射液为澄清黄色液体,每100 mL溶液中均匀分布有10 g ADP。其pH值和药物含量分别约为6.20和99.35%~100.40%。质量评估初步表明其质量可靠且稳定。此外,本研究首次应用支气管肺泡灌洗法评估感染部位的准确ADP浓度。通过药效学测定,ADP对CVCC 607的MIC、MBC和MPC分别为2 μg/mL、4 μg/mL和12.8 μg/mL。细菌生长抑制曲线表明,ADP是一种浓度依赖性抗菌药物,并选择了AUC/MIC的PK-PD模型参数。通过WinNonlin软件评估的肺泡液药代动力学参数显示,ADP在健康猪和感染猪中的药代动力学过程相似。结合药代动力学-药效学(PK-PD)建模,可采用4.10 mg/kg或5.91 mg/kg、每12 h一次、持续3至5天的给药方案来治疗[感染类型]感染。因此,这种多剂量方案的ADP注射液将是一种有前景的抗菌产品,可有效治疗猪的[感染类型]感染。