{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:47:10Z","timestamp":1782485230549,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"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"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The beta\u2010lactam antibiotic temocillin is increasingly used to treat extended\u2010spectrum beta\u2010lactamase (ESBL\u2010producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The plasma pharmacokinetics were analysed using non\u2010linear mixed\u2010effects modelling. Data from individuals in four groups: healthy volunteers (HV), urinary tract infection patients (UTI), ventriculitis patients and sepsis\u2010ICU patients were included. Simulations were performed to compare the PTA for different dosing regimens and participant\u2010groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A two\u2010compartment protein\u2010binding model best fitted the 1085 concentrations (543 unbound, 542 total). Temocillin clearance was influenced by creatinine clearance, serum albumin (ALB) and C\u2010reactive protein (CRP). For 2\u00a0g q8h intermittent infusion, the PTAs at an MIC of 16\u2009mg\/L were 2.3%, 39.5%, 10.0% and 72.5%, for HV, UTI, ventriculitis and sepsis\u2010ICU patients, respectively. The effects of the covariates on the PTA were simulated for two example patients with intermittent infusion: the PTAs at an MIC of 8\u00a0mg\/L for a sepsis\u2010ICU patient (CRP 300\u2009mg\/L, albumin 15\u2009g\/L) and a mild\u2010UTI patient (CRP 30\u2009mg\/L, albumin 35\u2009g\/L) were 94.3% and 62.4%, respectively. Continuous infusion consistently outperformed intermittent infusion in achieving the desired pharmacodynamic target (time above MIC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study underscores the significant variation in temocillin clearance and unbound fractions among different participant groups, challenging the efficacy of traditional 2\u00a0g q12h dosing. For patients with enhanced renal function and lower inflammation, continuous infusion emerges as a more effective strategy to achieve optimal target attainment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.16397","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T07:03:15Z","timestamp":1737529395000},"page":"1716-1726","source":"Crossref","is-referenced-by-count":1,"title":["Variable temocillin protein binding and pharmacokinetics in different clinical conditions: Implications for target attainment"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4692-9689","authenticated-orcid":false,"given":"Letao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrin","family":"Ngougni Pokem","sequence":"additional","affiliation":[{"name":"Pharmacologie cellulaire et mol\u00e9culaire, Louvain Drug Research Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan D. 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