{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:24:34Z","timestamp":1791919474440,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T00:00:00Z","timestamp":1344211200000},"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":[[2012,9]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Response to allopurinol in patients with gout is often suboptimal due to large variability in pharmacokinetics.<\/jats:p><jats:p>\u2022\u2003The sources of the variability in oxypurinol pharmacokinetics have not been systematically identified and quantified.<\/jats:p><jats:p>\u2022\u2003A therapeutic target 15\u201323\u2003mg\u2003l<jats:sup>\u22121<\/jats:sup>for oxypurinol concentrations has recently been established.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Renal function and concomitant diuretic\/probenecid use significantly influence oxypurinol pharmacokinetics.<\/jats:p><jats:p>\u2022\u2003This model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degrees of renal impairment.<\/jats:p><jats:p>\u2022\u2003Model predictions show a failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold>Our aim was to identify and quantify the sources of variability in oxypurinol pharmacokinetics and explore relationships with plasma urate concentrations.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold>Non\u2010linear mixed effects modelling was applied to concentration\u2013time data from 155 gouty patients with demographic, medical history and renal transporter genotype information.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>A one compartment pharmacokinetic model with first order absorption best described the oxypurinol concentration\u2013time data. Renal function and concomitant medicines (diuretics and probenecid), but not transporter genotype, significantly influenced oxypurinol pharmacokinetics and reduced the between subject variability in the apparent clearance of oxypurinol (CL\/<jats:italic>F<\/jats:italic><jats:sub>m<\/jats:sub>) from 65% to 29%. CL\/<jats:italic>F<\/jats:italic><jats:sub>m<\/jats:sub>for patients with normal, mild, moderate and severe renal impairment was 1.8, 0.6, 0.3 and 0.18\u2003l\u2003h<jats:sup>\u22121<\/jats:sup>, respectively. Model predictions showed a relationship between plasma oxypurinol and urate concentrations and failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold>In conclusion, this first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degrees of renal impairment.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2012.04207.x","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T14:57:04Z","timestamp":1328194624000},"page":"477-489","source":"Crossref","is-referenced-by-count":32,"title":["The pharmacokinetics of oxypurinol in people with gout"],"prefix":"10.1111","volume":"74","author":[{"given":"Sophie L.","family":"Stocker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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