Infectious Disease Pharmacokinetics Laboratory, College of Pharmacy, Emerging Pathogens Institute, University of Florida, Gainesville, Florida; and.
Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
Ther Drug Monit. 2020 Feb;42(1):129-132. doi: 10.1097/FTD.0000000000000675.
The mortality rate of patients with a drug-resistant bacterial infection is high, as are the associated treatment costs. To overcome these issues, optimization of the available therapeutic options is required. Beta-lactams are time-dependent antibiotics and their efficacy is determined by the amount of time the free concentration remains above the minimum inhibitory concentration. Therefore, the aim of this study was to assess the extent and variability of protein binding for meropenem, cefepime, and piperacillin.
Plasma samples for the analysis of meropenem, cefepime, and piperacillin were collected from patients admitted to a tertiary care hospital as part of the standard care. The bound and unbound drug fractions in the samples were separated by ultrafiltration. Validated liquid chromatography-tandem mass spectrometry assays were used to quantify the total and free plasma concentrations, and the protein binding was determined.
Samples from 95 patients were analyzed. The median (range) age of patients was 56 years (17-87) and the median (range) body mass index was 25.7 kg/m (14.7-74.2). Approximately 59% of the patients were men. The median (range) unbound fraction (fu) was 62.5% (41.6-99.1) for meropenem, 61.4% (51.6-99.2) for cefepime, and 48.3% (39.4-71.3) for piperacillin. In the bivariate analysis, as the total meropenem concentration increased, the fu increased (r = 0.37, P = 0.045). A decrease in piperacillin fu was observed as the albumin concentration increased (r = -0.56, P = 0.005).
The average fu values were lower than those reported in the literature. There was also a large variability in fu; hence, it should be considered when managing patients administered with these drugs through direct measurements of free drug concentrations.
耐药菌感染患者的死亡率高，治疗费用也高。为了克服这些问题，需要优化现有的治疗选择。β-内酰胺类是时间依赖性抗生素，其疗效取决于游离浓度超过最低抑菌浓度的时间量。因此，本研究旨在评估美罗培南、头孢吡肟和哌拉西林的蛋白结合程度和可变性。
从三级护理医院住院患者中采集用于分析美罗培南、头孢吡肟和哌拉西林的血浆样本，作为标准护理的一部分。通过超滤分离样本中的结合和未结合药物部分。使用经过验证的液相色谱-串联质谱法测定总血浆浓度和游离血浆浓度，并确定蛋白结合率。
分析了 95 名患者的样本。患者的中位（范围）年龄为 56 岁（17-87 岁），中位（范围）体重指数为 25.7 kg/m²（14.7-74.2）。大约 59%的患者为男性。美罗培南的中位（范围）未结合分数（fu）为 62.5%（41.6-99.1），头孢吡肟为 61.4%（51.6-99.2），哌拉西林为 48.3%（39.4-71.3）。在二元分析中，随着美罗培南总浓度的增加，fu 增加（r = 0.37，P = 0.045）。随着白蛋白浓度的增加，哌拉西林 fu 下降（r = -0.56，P = 0.005）。
平均 fu 值低于文献报道值。fu 也存在很大的变异性，因此在通过直接测量游离药物浓度来管理使用这些药物的患者时，应考虑这一点。
