{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:24:27Z","timestamp":1791919467002,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T00:00:00Z","timestamp":1567468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>The aims of this study were to determine factors that predict serum urate (<jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content>) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24\u2010month open, randomized, controlled, parallel\u2010group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and <jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content> was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic (<jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content>) curves were used to identify a minimum oxypurinol concentration predictive of <jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content> &lt;\u00a06\u00a0mg\/dL. There was a wide range of SU concentrations for each allopurinol dose. The relationship between sensitivity to allopurinol and allopurinol metabolism for each 100\u00a0mg allopurinol dose increase varied between individuals. Body mass index (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.023), creatinine clearance (Cr<jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>;<jats:italic> P<\/jats:italic>\u00a0=\u00a00.037), <jats:italic>ABCG2 <\/jats:italic>Q141K (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.019), and <jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.004) were associated with sensitivity to allopurinol. The minimum oxypurinol concentration for achieving the urate target was found to be about 104\u00a0\u03bcmol\/L, but predictive accuracy was poor (<jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content> curve area under the curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>) 0.65). The minimum therapeutic oxypurinol concentration was found to increase with decreasing renal function. Although there is a positive relationship between change in oxypurinol and change in SU concentration, a minimum therapeutic oxypurinol is dependent on Cr<jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content> and cannot reliably predict SU target. Other variables, including <jats:italic><jats:styled-content style=\"fixed-case\">ABCG<\/jats:styled-content><\/jats:italic>2 Q141K genotype, impact on sensitivity to allopurinol (<jats:styled-content style=\"fixed-case\">ACTRN<\/jats:styled-content>12611000845932).<\/jats:p>","DOI":"10.1111\/cts.12686","type":"journal-article","created":{"date-parts":[[2019,8,24]],"date-time":"2019-08-24T02:29:35Z","timestamp":1566613775000},"page":"110-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Relationships Between Allopurinol Dose, Oxypurinol Concentration and Urate\u2010Lowering Response\u2014In Search of a Minimum Effective Oxypurinol Concentration"],"prefix":"10.1111","volume":"13","author":[{"given":"Lisa K.","family":"Stamp","sequence":"first","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"},{"name":"Department of Rheumatology, Immunology, and Allergy Christchurch Hospital Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Immunology, and Allergy Christchurch Hospital Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Barclay","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Horne","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Frampton","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony R.","family":"Merriman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F. B.","family":"Wright","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,3]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21772"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209707"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key237"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12126"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13516"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12799"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex467"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315424"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/26.6.445"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.113"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210872"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211873"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30119"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.89"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2017.11.002"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2018.09.002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1439"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210661"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12686","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12686","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12686","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T20:41:34Z","timestamp":1694032894000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,3]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/cts.12686"],"URL":"https:\/\/doi.org\/10.1111\/cts.12686","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,3]]},"assertion":[{"value":"2019-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}