Microdialysis Study of Aztreonam-Avibactam Distribution in Peritoneal Fluid and Muscle of Rats with or without Experimental Peritonitis
Microdialysis Study of Aztreonam-Avibactam Distribution in Peritoneal Fluid and Muscle of Rats with or without Experimental Peritonitis
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DOI：
10.1128/aac.01228-18
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发表时间：
2018-10-01
影响因子：
4.9
通讯作者：
Marchand, Sandrine
中科院分区：
文献类型：
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作者：
Chauzy, Alexia;Lamarche, Isabelle;Marchand, Sandrine
本研究的目的是通过微透析法研究氨曲南(ATM)和阿维巴坦(AVI)在腹膜炎和非腹膜炎大鼠腹腔液和肌肉间质液中的分布，并比较组织中的游离浓度和血液中的游离浓度。将微透析探头插入对照组(n=5)和盲肠结扎穿刺法造成的腹内脓毒症大鼠(n=9)的颈静脉、后腿肌肉和腹膜腔内。用药物反透析法测定两种分子在每种介质中的ATM和AVI探针回收率。ATM-AVI联合静脉推注，剂量为100-25 mg。Kg(-1)。收集120分钟以上的微透析样品，用液相色谱-串联质谱仪测定ATM-AVI浓度。进行非室药代动力学分析，并使用非参数检验进行感染组与对照组之间的统计比较。在对照组和腹膜炎大鼠，ATM和AVI在腹腔液和肌肉中的分布迅速而完整，而在对照组和感染动物中，ATM和AVI在血液、腹腔液和肌肉中的浓度分布几乎是重叠的。在对照和感染动物中，未结合的组织细胞外液和曲线下的系统区域之间没有统计学上的显著差异。在本研究中，盲肠结扎和穿孔所致的腹腔感染对大鼠ATM和AVI的药代动力学无明显影响。
The purpose of this study was to investigate aztreonam (ATM) and avibactam (AVI) distribution in intraperitoneal fluid and muscle interstitial fluid by microdialysis in rats, with or without peritonitis, and to compare the unbound concentrations in tissue with the unbound concentrations in blood. Microdialysis probes were inserted into the jugular veins, hind leg muscles, and peritoneal cavities of control rats (n = 5) and rats with intra-abdominal sepsis (n = 9) induced by cecal ligation and punctures. ATM and AVI probe recoveries in each medium were determined for both molecules in each rat by retrodialysis by drug. ATM-AVI combination was administered as an intravenous bolus at a dose of 100-25 mg . kg(-1). Microdialysis samples were collected over 120 min, and ATM-AVI concentrations were determined by liquid chromatography-tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was conducted and nonparametric tests were used for statistical comparisons between groups (infected versus control) and medium. ATM and AVI distribution in intraperitoneal fluid and muscle was rapid and complete both in control rats and in rats with peritonitis, and the concentration profiles in blood, intraperitoneal fluid, and muscle were virtually superimposed, in control and infected animals, both for ATM and AVI. No statistically significant difference was observed between unbound tissue extracellular fluid and systemic areas under the curve for both molecules in control and infected animals. In the present study, intraperitoneal infection induced by cecal ligation and puncture had no apparent effect on ATM and AVI pharmacokinetics in rats.