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微透析法测定头孢喹肟在健康、中性粒细胞减少和感染小鼠大腿中的药代动力学

Microdialysis Determination of Cefquinome Pharmacokinetics in Murine Thigh From Healthy, Neutropenic, and Infected Mice.

作者信息

Zhang Longfei, Yao Lihua, Kang Zheng, Huang Zilong, Gu Xiaoyan, Shen Xiangguang, Ding Huanzhong

机构信息

Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.

出版信息

Front Pharmacol. 2019 Mar 12;10:249. doi: 10.3389/fphar.2019.00249. eCollection 2019.

Abstract

This study was aimed at applying microdialysis to explore cefquinome pharmacokinetics in thigh and plasma of healthy, neutropenic, and -infected mice. The relative recoveries (RRs) were tested by dialysis and retrodialysis and by retrodialysis. ICR mice were randomly divided into four groups: H-40 (healthy mice receiving cefquinome at 40 mg/kg), H-160, N-40 (neutropenic mice), and I-40 mg/kg (thigh infected-mice with ). After cefquinome administration, plasma was collected by retro-orbital puncture and thigh dialysate was collected by using a microdialysis probe with Ringer's solution at a perfusion rate of 1.5 μL/min. Plasma and thigh dialysate samples were assessed by HPLC-MS/MS and analyzed by a non-compartment model. The mean recoveries in the thigh were 39.35, 38.59, and 37.29% for healthy, neutropenic, and infected mice, respectively. The mean plasma protein-binding level was 16.40% and was independent of drug concentrations. For all groups, the mean values of the free AUC in plasma were higher than those in murine thigh, while the elimination for plasma were lower than those for murine thigh. Cefquinome penetration (AUC/AUC) from the plasma to thigh was 0.76, 0.88, 0.47, and 0.98 for H-40, N-40, I-40, and H-160 mg/kg, respectively. These results indicated that infection significantly affected cefquinome pharmacokinetics in murine thigh. In conclusion, we successfully applied a microdialysis method to evaluate the pharmacokinetics of cefquinome in murine thigh of healthy, neutropenic, and -infected mice and the pharmacokinetics of cefquinome was obviously affected by infection in thigh.

摘要

本研究旨在应用微透析技术探讨头孢喹肟在健康、中性粒细胞减少和感染小鼠的大腿组织及血浆中的药代动力学。通过透析、反透析和再反透析检测相对回收率(RRs)。将ICR小鼠随机分为四组:H-40(接受40mg/kg头孢喹肟的健康小鼠)、H-160、N-40(中性粒细胞减少小鼠)和I-40mg/kg(大腿感染小鼠)。给予头孢喹肟后,通过眶后穿刺采集血浆,使用灌注速率为1.5μL/min的林格氏液微透析探针采集大腿透析液。血浆和大腿透析液样本采用高效液相色谱-串联质谱法(HPLC-MS/MS)进行评估,并采用非房室模型进行分析。健康、中性粒细胞减少和感染小鼠大腿的平均回收率分别为39.35%、38.59%和37.29%。平均血浆蛋白结合水平为16.40%,且与药物浓度无关。对于所有组,血浆中游离血药浓度-时间曲线下面积(AUC)的平均值高于小鼠大腿中的值,而血浆中的消除率低于小鼠大腿中的值。H-40、N-40、I-40和H-160mg/kg组从血浆到大腿的头孢喹肟渗透系数(AUC/AUC)分别为0.76、0.88、0.47和0.98。这些结果表明,感染显著影响头孢喹肟在小鼠大腿中的药代动力学。总之,我们成功应用微透析方法评估了头孢喹肟在健康、中性粒细胞减少和感染小鼠大腿中的药代动力学,且大腿感染明显影响头孢喹肟的药代动力学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f5/6422941/8ef7a1ce252b/fphar-10-00249-g001.jpg

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