{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:06:24Z","timestamp":1768266384133,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"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":[[2020,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To examine the pharmacokinetic\u2010phamacodynamic (PK\u2010PD) relationships of plasma febuxostat and serum urate and the effect of a single dose of the drug on renal excretion and fractional clearance of urate (FCU).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood and urine samples were collected at baseline and up to 145 hours following administration of febuxostat (80 mg) to healthy subjects (n = 9). Plasma febuxostat and serum and urinary urate and creatinine concentrations were determined. Febuxostat pharmacokinetics were estimated using a two\u2010compartment model with first\u2010order absorption. An Emax PK\u2010PD model was fitted to mean febuxostat and urate concentrations. Urinary urate excretion and FCU were calculated pre\u2010 and post\u2010dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maximum mean plasma concentration of febuxostat (2.7 mg L<jats:sup>\u22121<\/jats:sup>) was observed 1.2 hours after dosage. Febuxostat initial and terminal half\u2010lives were 2.0 \u00b1 1.0 and 14.0 \u00b1 4.7 hours (mean \u00b1 SD), respectively. The majority (81%) of the drug was eliminated in the 9 hours after dosing. Serum urate declined slowly achieving mean nadir (0.20 mmol L<jats:sup>\u22121<\/jats:sup>) at 24 hours. The IC<jats:sub>50<\/jats:sub> (plasma febuxostat concentration that inhibits urate production by 50%) was 0.11 \u00b1 0.09 mg L<jats:sup>\u22121<\/jats:sup> (mean \u00b1 SD). Urinary urate excretion changed in parallel with serum urate. There was no systematic or significant change in FCU from baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The PK\u2010PD model could potentially be used to individualise febuxostat treatment and improve clinical outcomes. A single dose of febuxostat does not affect the efficiency of the kidney to excrete urate. Further investigations are required to confirm the present results following multiple dosing with febuxostat.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14357","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T12:35:15Z","timestamp":1589027715000},"page":"2486-2496","source":"Crossref","is-referenced-by-count":8,"title":["A pharmacokinetic\u2010pharmacodynamic study of a single dose of febuxostat in healthy subjects"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7993-8776","authenticated-orcid":false,"given":"Bishoy","family":"Kamel","sequence":"first","affiliation":[{"name":"The George Institute for Global Health  Australia"},{"name":"St Vincent's Clinical School University of New South Wales  Australia"},{"name":"Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital  Sydney New South Wales Australia"},{"name":"School of Medical Sciences University of New South Wales  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