Department of Medicine, University of Otago, Christchurch, New Zealand.
Department of Clinical Pharmacology, Canterbury District Health Board, Christchurch, New Zealand.
Br J Clin Pharmacol. 2018 Oct;84(10):2311-2316. doi: 10.1111/bcp.13673. Epub 2018 Jul 20.
Flucloxacillin dosing may be guided by measurement of its total plasma concentrations. Flucloxacillin is highly protein bound with fraction unbound in plasma (f ) of around 0.04 in healthy individuals. The utility of measuring unbound flucloxacillin concentrations for patients outside the intensive care unit (ICU) is not established. We aimed to compare flucloxacillin f in non-ICU hospitalised patients against healthy volunteers, and to examine the performance of a published model for predicting unbound concentrations, using total flucloxacillin and plasma albumin concentrations.
Data from 12 healthy volunteers (248 samples) and 47 hospitalized patients (61 samples) were examined. Plasma flucloxacillin concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. Flucloxacillin f for the two groups was compared using a generalized estimating equation model to account for clustered observations. The performance of the single protein binding site prediction model in hospitalized patients was compared with measured unbound concentrations using Bland-Altman plots.
The median (range) flucloxacillin f for healthy (median albumin 45 g l ) and hospitalized individuals (median albumin 30 g l ) were 0.04 (0.02-0.07) and 0.10 (0.05-0.37), respectively (P < 0.0001). The prediction model underpredicted unbound flucloxacillin concentrations with a mean bias (95% limits of agreement) of -54% (-137%, +30%).
The flucloxacillin f values observed in our cohort of hospitalized patients had a wide range and were greater than those of healthy individuals. Unbound flucloxacillin plasma concentrations were predicted poorly by the model. Instead, unbound concentrations should be measured to guide dosing.
氟氯西林的剂量可以通过测量其总血浆浓度来指导。氟氯西林与血浆中未结合的部分（f）高度结合，在健康个体中约为 0.04。对于重症监护病房（ICU）以外的患者，测量未结合氟氯西林浓度的实用性尚未确定。我们旨在比较非 ICU 住院患者与健康志愿者的氟氯西林 f，并使用总氟氯西林和血浆白蛋白浓度来检验预测未结合浓度的已发表模型的性能。
检查了 12 名健康志愿者（248 个样本）和 47 名住院患者（61 个样本）的数据。使用经过验证的液相色谱-串联质谱法测量血浆氟氯西林浓度。使用广义估计方程模型比较两组的氟氯西林 f，以解释聚类观察。使用 Bland-Altman 图比较住院患者中单蛋白结合位点预测模型与实测未结合浓度的性能。
健康组（中位数白蛋白 45 g/L）和住院组（中位数白蛋白 30 g/L）的氟氯西林 f 的中位数（范围）分别为 0.04（0.02-0.07）和 0.10（0.05-0.37）（P < 0.0001）。预测模型低估了未结合氟氯西林浓度，平均偏差（95%置信区间）为-54%（-137%，+30%）。
我们的住院患者队列中观察到的氟氯西林 f 值范围很广，大于健康个体。该模型对未结合氟氯西林血浆浓度的预测能力较差。相反，应测量未结合浓度以指导剂量。
