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猪对抗生素的选择性和集中性肠肝循环

Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs.

作者信息

Buddington Karyl K, Pierzynowski Stefan G, Holmes William E, Buddington Randal K

机构信息

Department of Biology, University of Memphis, Memphis, TN 38152, USA.

Department of Biology, Lund University, Sölvegatan 35, 22362 Lund, Sweden.

出版信息

Antibiotics (Basel). 2023 Dec 21;13(1):12. doi: 10.3390/antibiotics13010012.

Abstract

Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography-mass spectroscopy in plasma and PES after enteral administration to juvenile pigs with jugular catheters and re-entrant pancreatic-duodenal catheters. Nystatin, which is not absorbed by the intestine nor used for infectious pancreatitis (negative control), was not detected in plasma or PES. Concentrations of amoxicillin increased in plasma after administration ( = 0.035), but not in PES ( = 0.51). Metronidazole and enrofloxacin that are used for infectious pancreatitis increased in plasma after enteral administration and even more so in PES, with concentrations in PES averaging 3.1 (±0.5)- and 2.3 (±0.6)-fold higher than in plasma, respectively ('s < 0.001). The increase in enrofloxacin in PES relative to plasma was lower after intramuscular administration (1.8 ± 0.5; = 0.001). The present results demonstrate the presence of a selective and concentrative enteropancreatic pathway of secretion for some antibiotics. Unlike the regulated secretion of bile, the constitutive secretion of PES and intestinal reabsorption may provide a continuous exposure of pancreas tissue and the small intestine to recirculated antibiotics and potentially other therapeutic molecules. There is a need to better understand the enteropancreatic recirculation of antibiotics and the associated mechanisms.

摘要

对感染性胰腺炎有效的抗生素在静脉给药后会出现在胰腺外分泌液(PES)中,且浓度高于最低抑菌浓度。我们通过串联液相色谱 - 质谱法测量了经肠内给药至带有颈静脉导管和再入式胰十二指肠导管的幼猪后,血浆和PES中四种抗生素的浓度。制霉菌素既不被肠道吸收,也不用于治疗感染性胰腺炎(阴性对照),在血浆或PES中均未检测到。阿莫西林给药后血浆浓度升高( = 0.035),但在PES中未升高( = 0.51)。用于治疗感染性胰腺炎的甲硝唑和恩诺沙星在肠内给药后血浆浓度升高,在PES中升高更为明显,PES中的浓度分别平均比血浆高3.1(±0.5)倍和2.3(±0.6)倍('s < 0.001)。肌肉注射后,恩诺沙星在PES中相对于血浆的升高幅度较小(1.8 ± 0.5; = 0.001)。目前的结果表明,某些抗生素存在选择性和浓缩性的肠胰分泌途径。与胆汁的调节性分泌不同,PES的组成性分泌和肠道重吸收可能使胰腺组织和小肠持续暴露于循环的抗生素以及潜在的其他治疗分子中。有必要更好地了解抗生素的肠胰循环及其相关机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1584/10812520/dd0e523110f5/antibiotics-13-00012-g002.jpg

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