Article date: October 2018
By: Paul Ken Leong Chin, Philip George Drennan, Sharon Jane Gardiner, Mei Zhang, Simon Charles Dalton, Stephen Thomas Chambers, Evan James Begg in Volume 84, Issue 10, pages 2311-2316
Aims
Flucloxacillin dosing may be guided by measurement of its total plasma concentrations. Flucloxacillin is highly protein bound with fraction unbound in plasma (fu) 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 fu 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.
Methods
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 fu 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.
Results
The median (range) flucloxacillin fu for healthy (median albumin 45 g l–1) and hospitalized individuals (median albumin 30 g l–1) 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%).
Conclusions
The flucloxacillin fu 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.
DOI: 10.1111/bcp.13673
View this article