Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
Ther Drug Monit. 2019 Jun;41(3):325-330. doi: 10.1097/FTD.0000000000000602.
Piperacillin is considered a moderately protein-bound antibiotic (20%-40%), with albumin being an important binding protein. Although infrequently used in practice, different methods to measure the fraction unbound (fu) are available, but uncertainty remains as to what the most appropriate method is. The main goal of this study was to estimate the impact of the methodology used to measure unbound piperacillin in plasma on the fu of piperacillin; we compared ultrafiltration (UF) at 4°C and 37°C with the reference method, equilibrium dialysis. In addition, we analyzed the impact of other proteins on the fu.
Anonymized left-over Li-heparin plasma samples (n = 41) from 30 critically ill patients who were treated with piperacillin were used for the analyses.
We found that the piperacillin fu, determined by UF, is on average 8% higher at 37°C (91%) than at 4°C (83%). There were no systematic or proportional differences between UF at 4°C and equilibrium dialysis at 4°C. This emphasizes the importance of the temperature during UF, which should therefore be clearly stated in publications that report on the methodology of UF. No significant impact of the albumin-, IgA-, total protein-, or α1-acid glycoprotein concentration on the fu was found. The fu found in this study was higher than the generally assumed fu value of 60%-80%. A possible explanation lies in the studied population or in the temperature used. Based on our results, routine monitoring of unbound piperacillin in intensive care unit patients is not recommended.
Based on the prediction model, we can state that in intensive care patients the fu of piperacillin is 91% (SD 7%), determined with UF at 37°C.
哌拉西林被认为是一种中等程度结合蛋白的抗生素（20%-40%），白蛋白是其重要的结合蛋白。尽管在实践中很少使用，但有不同的方法来测量未结合分数（fu），但仍不确定哪种方法最合适。本研究的主要目的是评估测量血浆中未结合哌拉西林的方法对哌拉西林 fu 的影响；我们比较了 4°C 和 37°C 的超滤（UF）与参考方法平衡透析。此外，我们还分析了其他蛋白对 fu 的影响。
使用来自 30 名接受哌拉西林治疗的危重症患者的匿名左肝素锂血浆样本（n = 41）进行分析。
我们发现，37°C 时 UF 测定的哌拉西林 fu 平均比 4°C 时高 8%（91%）。UF 在 4°C 时与平衡透析在 4°C 时之间没有系统或比例差异。这强调了 UF 过程中温度的重要性，因此在报告 UF 方法的出版物中应明确说明温度。白蛋白、IgA、总蛋白或α1-酸性糖蛋白浓度对 fu 没有显著影响。本研究中发现的 fu 值高于通常假设的 60%-80%的 fu 值。一种可能的解释在于所研究的人群或所使用的温度。基于我们的结果，不建议常规监测 ICU 患者的未结合哌拉西林。
根据预测模型，我们可以说在重症监护患者中，37°C 时 UF 测定的哌拉西林 fu 为 91%（SD 7%）。
