{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:43:03Z","timestamp":1776411783505,"version":"3.51.2"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"grants from Region Stockholm","award":["FoUI-954900"],"award-info":[{"award-number":["FoUI-954900"]}]},{"name":"grants from Region Stockholm","award":["FoUI-973467"],"award-info":[{"award-number":["FoUI-973467"]}]},{"name":"grants from Region Stockholm","award":["FoUI-974859"],"award-info":[{"award-number":["FoUI-974859"]}]},{"name":"Vinnova\/Platinea","award":["2021-02699"],"award-info":[{"award-number":["2021-02699"]}]},{"DOI":"10.13039\/501100009228","name":"Region \u00d6rebro County","doi-asserted-by":"publisher","award":["OLL-983304"],"award-info":[{"award-number":["OLL-983304"]}],"id":[{"id":"10.13039\/501100009228","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the population pharmacokinetics of unbound cloxacillin in patients undergoing total arthroplasty of the hip (THA) or knee (TKA), and to explore alternative dosing regimens for cloxacillin prophylaxis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma concentrations of total and unbound cloxacillin from 200 patients undergoing primary elective THA (n\u200a&amp;\u200a95) or TKA (n\u200a&amp;\u200a105) were analysed. Intravenous cloxacillin doses of 2\u2005g were administered pre-surgery, and repeated after 2 and 6\u2005hours. Samples (n\u200a&amp;\u200a496) were analysed using HPLC-MS\/MS. Non-linear mixed-effects modelling was performed to develop a population pharmacokinetic model describing unbound cloxacillin exposure. Using this model, alternative prophylaxis regimens were explored with Monte Carlo simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A two-compartment model with non-linear protein binding adequately described the data. Estimated glomerular filtration rate (eGFR) and body weight (kg) were significant covariates on unbound cloxacillin clearance. In 13% of patients sampled at the end of surgery (n\u200a&amp;\u200a25\/187), unbound cloxacillin &amp;lt;2\u2005mg\/L was observed. A model-predicted 18\u201322% (n\u200a&amp;\u200a36\u201343\/200) of patients failed to sustain plasma levels \u22652\u2005mg\/L throughout the two-hour dosing interval with the current regimen. In contrast, a continuous 1\u2005g\/h infusion after a 1\u2005g loading dose would ensure target attainment in &amp;gt;99% of patients, according to the model predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>For many THA and TKA patients, the current cloxacillin prophylaxis regimen may fail to provide adequate target site concentrations during the entire surgical procedure. Transitioning to a prolonged infusion protocol could increase attainment of PK\/PD targets without exceeding the currently recommended total perioperative dose amounts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag116","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:45:48Z","timestamp":1775043948000},"source":"Crossref","is-referenced-by-count":0,"title":["Optimizing cloxacillin prophylaxis in hip and knee arthroplasty based on population pharmacokinetics of unbound plasma concentrations"],"prefix":"10.1093","volume":"81","author":[{"given":"Gustaf","family":"Beijer","sequence":"first","affiliation":[{"name":"Medical Unit of Clinical Pharmacology, MDK, Karolinska University Hospital , Stockholm ,","place":["Sweden"]},{"name":"Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet , Stockholm 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Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Department of Global Public Health, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Eliasson","sequence":"additional","affiliation":[{"name":"Medical Unit of Clinical Pharmacology, MDK, Karolinska University Hospital , Stockholm ,","place":["Sweden"]},{"name":"Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"2026041702463751500_dkag116-B1","author":"European Centre for Disease Prevention and Control (ECDC)"},{"key":"2026041702463751500_dkag116-B2","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1302\/0301-620X.98B8.37359","article-title":"Antibiotic prophylaxis in orthopaedic surgery: difficult decisions in an 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