Nosek Krzysztof, Samiec Milena, Ziółkowski Hubert, Markowska-Buńka Paulina, Czuczwar Mirosław, Borys Michał, Onichimowski Dariusz
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Warmia and Mazury, Al. Warszawska 30, 10-082 Olsztyn, Poland.
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, University of Warmia and Mazury, Al. Warszawska 30, 11-082 Olsztyn, Poland.
Pharmaceuticals (Basel). 2024 Oct 2;17(10):1317. doi: 10.3390/ph17101317.
Renal replacement therapy (RRT), widely used in the treatment of renal injury during sepsis, aims to eliminate the toxins and proinflammatory cytokines involved in the pathomechanism underlying septic shock. Dialysis filters are characterized by a high adsorption potential for cytokines in RRT in the case of septic renal injury. For the treatment of sepsis with antibiotics, it is of key importance to achieve the desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid on three different types of filters used in CRRT. In our in vitro study, a continuous veno-venous hemofiltration (CVVH) was conducted using three types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI), and non-PEI-treated polyacrylonitrile (PAN). Each type of filter was used in three CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 mL of bovine blood or in 700 mL of 0.9% NaCl. In each case, the total volume of the obtained solution was 1000 mL. Blood samples were collected at particular time points to measure their drug concentration. The differences in mean drug/NaCl adsorption and drug/blood adsorption were determined using a one-way ANOVA with multiple comparisons via Tukey's post hoc test; a -value of <0.05 was considered significant. : A significant adsorption of linezolid was found for PAN PEI filters, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. In PAN PEI samples, the concentration of linezolid in 0.9% NaCl solutions decreased from 594.74 μg/mL to 310.66 μg/mL after 120 min (the difference was established at 52%). In blood samples, the initial concentration was 495.18 μg/mL, which then decreased to 359.84 μg/mL (73% of the beginning value). No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.
肾脏替代疗法（RRT）广泛应用于脓毒症期间肾损伤的治疗，旨在清除参与脓毒性休克发病机制的毒素和促炎细胞因子。在脓毒性肾损伤的情况下，透析滤器在RRT中对细胞因子具有高吸附潜力。对于使用抗生素治疗脓毒症，实现PK/PD指数的理想值至关重要。连续性肾脏替代疗法（CRRT）可能会影响抗菌药物清除率，在某些情况下会增加其清除。本研究的目的是确定利奈唑胺在CRRT中使用的三种不同类型滤器上的吸附程度。在我们的体外研究中，使用三种类型的滤器进行连续性静脉-静脉血液滤过（CVVH）：聚砜（PS）、聚乙烯亚胺处理的聚丙烯腈（PAN PEI）和未用PEI处理的聚丙烯腈（PAN）。每种类型的滤器在三个CVVH循环中使用，其中涉及将600mg利奈唑胺溶解在700mL牛血或700mL 0.9%氯化钠中。在每种情况下，所得溶液的总体积为1000mL。在特定时间点采集血样以测量其药物浓度。使用单向方差分析和通过Tukey事后检验进行多重比较来确定平均药物/氯化钠吸附和药物/血液吸附的差异；P值<0.05被认为具有统计学意义。结果：在终点时，发现PAN PEI滤器对利奈唑胺有显著吸附，无论是从牛血还是0.9%氯化钠溶液中获得的样品。在PAN PEI样品中，120分钟后0.9%氯化钠溶液中利奈唑胺的浓度从594.74μg/mL降至310.66μg/mL（差异确定为52%）。在血样中，初始浓度为495.18μg/mL，然后降至359.84μg/mL（初始值的73%）。在PAN或PS滤器上未显示出显著吸附。需要进行体内研究以证实滤器类型对接受CRRT患者体内利奈唑胺浓度的影响。
