{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:58:53Z","timestamp":1788029933005,"version":"build-2784847793"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Flucloxacillin dosing may be guided by measurement of its total plasma concentrations. Flucloxacillin is highly protein bound with fraction unbound in plasma (f<jats:sub>u<\/jats:sub>) 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<jats:sub>u<\/jats:sub> in non\u2010ICU 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2013tandem mass spectrometry method. Flucloxacillin f<jats:sub>u<\/jats:sub> 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\u2013Altman plots.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median (range) flucloxacillin f<jats:sub>u<\/jats:sub> for healthy (median albumin 45\u00a0g\u00a0l<jats:sup>\u20131<\/jats:sup>) and hospitalized individuals (median albumin 30\u00a0g\u00a0l<jats:sup>\u20131<\/jats:sup>) were 0.04 (0.02\u20130.07) and 0.10 (0.05\u20130.37), respectively (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). The prediction model underpredicted unbound flucloxacillin concentrations with a mean bias (95% limits of agreement) of \u201354% (\u2013137%, +30%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The flucloxacillin f<jats:sub>u<\/jats:sub> 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13673","type":"journal-article","created":{"date-parts":[[2018,6,16]],"date-time":"2018-06-16T12:44:26Z","timestamp":1529153066000},"page":"2311-2316","source":"Crossref","is-referenced-by-count":13,"title":["Total flucloxacillin plasma concentrations poorly reflect unbound concentrations in hospitalized patients with <scp><i>Staphylococcus aureus<\/i><\/scp> bacteraemia"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-5191","authenticated-orcid":false,"given":"Paul Ken Leong","family":"Chin","sequence":"first","affiliation":[{"name":"Department of Medicine University of Otago  Christchurch New Zealand"},{"name":"Department of Clinical Pharmacology Canterbury District Health Board  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3367-3335","authenticated-orcid":false,"given":"Philip George","family":"Drennan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Canterbury District Health Board  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon Jane","family":"Gardiner","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacist, Departments of Clinical Pharmacology, Infectious Diseases and Pharmacy Christchurch Hospital  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago, Christchurch, and Toxicology, Canterbury Health Laboratories  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Charles","family":"Dalton","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Christchurch Hospital  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Thomas","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan James","family":"Begg","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago  Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"BennettJE DolinR BlaserMJ.Principles and practice of infectious diseases: Elsevier Health Sciences 2014."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200038030-00005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt523"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2009.tb02841.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00951-13"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/11595650-000000000-00000"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01833876"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3923\/jbs.2006.167.172"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4172\/2155-9872.1000196","article-title":"Determination of total and free concentrations of Flucloxacillin and cefazolin in human plasma by liquid chromatography\/tandem mass spectrometry","volume":"5","author":"Zhang M","year":"2014","journal-title":"J Anal Bioanal Tech"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/73.1.13"},{"key":"e_1_2_8_13_1","unstructured":"US Food and Drug Administration.Guidance for industry: bioanalytical method validation.2001."},{"key":"e_1_2_8_14_1","unstructured":"The European committee on antimicrobial susceptibility testing. 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