The aim of this study was to investigate the penetration of cefepime into rat peritoneal fluid by microdialysis and to determine the relationship between unbound drug plasma and tissue concentration in healthy animals and in a sepsis model established through cecal ligation and puncture‐induced peritonitis. Probe recovery was performed by dialysis and retrodialysis. Cefepime was administered at a dose of 110 mg/kg intravenously. Samples were collected for about 4 h, and concentrations were determined by liquid chromatography‐electrospray ionization‐QTOF MS. Tissue penetration was also determined. Probe recovery in vivo was 38.78% ± 3.31% and 38.83% ± 2.74% in the control and peritonitis groups, respectively. Cefepime was rapidly distributed in the peritoneal fluid in both groups. The peritoneal fluid/plasma cefepime ratio was 0.38 and 0.32 for the control and peritonitis groups, respectively. Cefepime concentrations were above the MIC of 4 mg/L for the main enterobacteria. The infection model that was used had no apparent effect on the pharmacokinetics of cefepime in rats. This was the first study to determine free cefepime concentrations in the peritoneal fluid of healthy rats and rats with experimental peritonitis.

中文翻译：

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通过微透析测定患有或不患有实验性腹膜炎的大鼠腹腔液中头孢吡肟的分布

本研究的目的是通过微透析研究头孢吡肟渗透到大鼠腹腔液中，并确定健康动物和通过盲肠结扎和穿刺诱发腹膜炎建立的脓毒症模型中未结合的药物血浆和组织浓度之间的关系。通过透析和逆透析进行探针回收。头孢吡肟以110mg/kg的剂量静脉注射。收集样品约4小时，并通过液相色谱-电喷雾电离-QTOF MS测定浓度。还测定了组织渗透性。探针恢复体内对照组和腹膜炎组的这一比例分别为 38.78% ± 3.31% 和 38.83% ± 2.74%。头孢吡肟在两组的腹腔液中均迅速分布。对照组和腹膜炎组的腹膜液/血浆头孢吡肟比率分别为0.38和0.32。头孢吡肟浓度高于主要肠道细菌的 4 mg/L MIC。使用的感染模型对头孢吡肟在大鼠中的药代动力学没有明显影响。这是第一项测定健康大鼠和实验性腹膜炎大鼠腹腔液中游离头孢吡肟浓度的研究。