{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:16:19Z","timestamp":1783476979497,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Oral flucloxacillin is widely used for methicillin\u2010susceptible\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      <\/jats:styled-content>\n                      (MSSA) infections, but its recommended 6\u2010hourly dosing may limit adherence. Probenecid inhibits renal tubular secretion of \u03b2\u2010lactams and enhances flucloxacillin exposure, allowing less frequent dosing. This study aimed to determine the effect of repeated dosing of probenecid on serum and urinary concentrations of flucloxacillin and its impact on pharmacodynamic target attainment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten healthy adults participated. Flucloxacillin was administered intravenously and orally. Oral flucloxacillin was administered with and without probenecid. Rich plasma sampling was undertaken, with analysis by UHPLC\u2013MS\/MS. A population PK model was developed and evaluated, followed by Monte Carlo simulations to assess the probability of target attainment (PTA; target of at least 50% fT\u2009&gt;\u2009MIC at MIC 0.5\u00a0mg\/L). Urinary biomarkers (NGAL, KIM\u20101, glycosaminoglycans), urinary flucloxacillin concentrations and serum creatinine concentrations were monitored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across 307 plasma samples, unbound steady state flucloxacillin concentrations were higher with probenecid (median 0.74\u2009mg\/L) than without (median 0.30\u2009mg\/L;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u2009.002). Probenecid reduced flucloxacillin clearance from 143 to 46.9\u00a0L\/h. Simulations showed markedly improved PTA for flucloxacillin 1\u00a0g 8\u00a0hourly with probenecid (84%) compared with 1\u00a0g 6\u00a0hourly alone (6%). Urinary flucloxacillin concentrations were reduced with probenecid, consistent with decreased renal clearance. Serum creatinine concentrations and urinary biomarkers remained stable, and only non\u2010serious adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Co\u2010administration of probenecid significantly enhanced flucloxacillin exposure, without serious adverse effects. These findings warrant evaluation in a clinical trial of patients with MSSA infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Clinical trial registered with ANZCTR: ACTRN12623001155684.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70663","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:20:39Z","timestamp":1783473639000},"source":"Crossref","is-referenced-by-count":0,"title":["Flucloxacillin plasma and urinary concentrations with and without probenecid and urinary biomarker profiles in healthy volunteers"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-1536","authenticated-orcid":false,"given":"Amy","family":"Legg","sequence":"first","affiliation":[{"name":"Menzies School of Health Research Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Department of Pharmacy Royal Brisbane and Women's Hospital  Brisbane Queensland Australia"},{"name":"University of Queensland Centre for Clinical Research, Faculty of Health Medicine and Behavioural Sciences The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Boast","sequence":"additional","affiliation":[{"name":"Antimicrobials Group, Murdoch Children's Research Institute The Royal Children's Hospital Melbourne  Parkville Victoria Australia"},{"name":"Infectious Diseases Department The Royal Children's Hospital Melbourne  Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Piera","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Charles Darwin University  Darwin Northern Territory Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health Medicine and Behavioural Sciences The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Wallis","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health Medicine and Behavioural Sciences The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Service The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity  Melbourne Australia"},{"name":"Department of Infectious Diseases The University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Davis","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Charles Darwin University  Darwin Northern Territory Australia"},{"name":"School of Medicine and Public Health and Hunter Medical Research Institute University of Newcastle  Newcastle Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Y. 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