Zhang Longfei, Zhou Zichong, Gu Xiaoyan, Huang Sixiu, Shen Xiangguang, Ding Huanzhong
College of Animal Science and Veterinary Medicine of Henan Institute of Science and Technology, Xinxiang, China.
Guangdong Provincial Key Laboratory of Veterinary Drugs Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.
Front Vet Sci. 2020 Aug 5;7:448. doi: 10.3389/fvets.2020.00448. eCollection 2020.
This study aimed to explore the application of microdialysis in pharmacokinetic (PK)/pharmacodynamic (PD) integration of cefquinome against . After the population reached 10 CFU/thigh, the mice received 0.04, 0.16, 0.63, 2.5, and 10 mg/kg cefquinome by subcutaneous injection. Plasma samples were collected by retro-orbital puncture for 4 h, and thigh dialysate was obtained by microdialysis at a flow rate of 1.5 μL/min for 6 h for the PK study. For the PD experiment, the infected mice were treated with a 4-fold-increase in the total cefquinome dose, ranging from 0.01 to 10 mg/kg/24 h, divided into one, two, three, four, and eight doses. The number of bacteria was determined and an inhibitory sigmoid maximum effect (E) model was used to analyse the relationships between PK/PD parameters and efficacy. The mean penetration of cefquinome from plasma to the thigh was 0.591. The PK data for PK/PD integration were obtained by extrapolation. The fittest PK/PD parameter for efficacy evaluation was %T>MIC (the percentage of time that free drug concentrations exceed the MIC). The magnitudes of %T>MIC to achieve net bacterial stasis, 1-log CFU reduction, 2-log CFU reduction, and 3-log CFU reduction were 19.56, 28.65, 41.59, and 67.07 % in plasma and 21.74, 36.11, 52.96, and 82.68% in murine thigh, respectively. Microdialysis was first applied to evaluate the PK/PD integration of cefquinome against . These results would provide valuable references when we apply microdialysis to study the PK/PD integration model and use cefquinome to treat animal diseases caused by .
本研究旨在探讨微透析技术在头孢喹肟药代动力学（PK）/药效学（PD）整合中的应用。当每只小鼠大腿的细菌数量达到10 CFU时，通过皮下注射给予小鼠0.04、0.16、0.63、2.5和10 mg/kg的头孢喹肟。通过眶后穿刺采集4小时的血浆样本，通过微透析以1.5 μL/分钟的流速获取6小时的大腿透析液用于PK研究。对于PD实验，感染小鼠接受总头孢喹肟剂量增加4倍的治疗，剂量范围为0.01至10 mg/kg/24小时，分为1、2、3、4和8剂。测定细菌数量，并使用抑制性S型最大效应（E）模型分析PK/PD参数与疗效之间的关系。头孢喹肟从血浆到大腿的平均渗透率为0.591。PK/PD整合的PK数据通过外推法获得。用于疗效评估的最适宜PK/PD参数是%T>MIC（游离药物浓度超过MIC的时间百分比）。在血浆中实现细菌净停滞、1-log CFU减少、2-log CFU减少和3-log CFU减少的%T>MIC值分别为19.56%、28.65%、41.59%和67.07%，在小鼠大腿中分别为21.74%、36.11%、52.96%和82.68%。首次应用微透析技术评估头孢喹肟的PK/PD整合情况。这些结果将为我们应用微透析技术研究PK/PD整合模型以及使用头孢喹肟治疗由……引起的动物疾病提供有价值的参考。 （注：原文中部分地方表述不完整，如“against.”，翻译时尽量根据已有内容准确呈现）
