{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:09:47Z","timestamp":1789524587279,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,28]],"date-time":"2017-05-28T00:00:00Z","timestamp":1495929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1054146"],"award-info":[{"award-number":["1054146"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000940","name":"Arthritis Australia","doi-asserted-by":"publisher","award":["Ray and Pam Robinson Award for Rheumatology"],"award-info":[{"award-number":["Ray and Pam Robinson Award for Rheumatology"]}],"id":[{"id":"10.13039\/501100000940","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of the study were to: 1) determine if a plasma oxypurinol <jats:italic>concentration<\/jats:italic>\u2013response relationship or an allopurinol <jats:italic>dose<\/jats:italic>\u2013response relationship best predicts the dose requirements of allopurinol in the treatment of gout; and 2) to construct a nomogram for calculating the optimum maintenance dose of allopurinol to achieve target serum urate (SU) concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A nonlinear regression analysis was used to examine the plasma oxypurinol <jats:italic>concentration\u2013<\/jats:italic> and allopurinol <jats:italic>dose<\/jats:italic>\u2013response relationships with serum urate. In 81 patients (205 samples), creatinine clearance (CL<jats:sub>CR<\/jats:sub>), concomitant diuretic use and SU concentrations before (U<jats:sub>P<\/jats:sub>) and during (U<jats:sub>T<\/jats:sub>) treatment were monitored across a range of allopurinol doses (D, 50\u2013700 mg daily). Plasma concentrations of oxypurinol (C) were measured in 47 patients (98 samples). Models (<jats:italic>n<\/jats:italic>\u00a0=\u00a047 patients) and predictions from each relationship were compared using <jats:italic>F<\/jats:italic>\u2010tests, <jats:italic>r<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup> values and paired <jats:italic>t<\/jats:italic>\u2010tests. The best model was used to construct a nomogram.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The final plasma oxypurinol <jats:italic>concentration<\/jats:italic>\u2013response relationship (<jats:styled-content><jats:italic>U<\/jats:italic><jats:sub><jats:italic>T<\/jats:italic><\/jats:sub>\u2009=\u2009<jats:italic>U<\/jats:italic><jats:sub><jats:italic>P<\/jats:italic><\/jats:sub>\u2009\u2013\u2009<jats:italic>C<\/jats:italic>*(<jats:italic>U<\/jats:italic><jats:sub><jats:italic>P<\/jats:italic><\/jats:sub>\u2009\u2013\u2009<jats:italic>U<\/jats:italic><jats:sub><jats:italic>R<\/jats:italic><\/jats:sub>)\/(<jats:italic>ID<\/jats:italic><jats:sub>50<\/jats:sub>\u2009+\u2009<jats:italic>C<\/jats:italic>)<\/jats:styled-content>, <jats:italic>r<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u00a0=\u00a00.64) and allopurinol <jats:italic>dose<\/jats:italic>\u2013response relationship (<jats:styled-content>U<jats:sub>T<\/jats:sub>\u2009=\u2009U<jats:sub>P<\/jats:sub>\u2009\u2013\u2009D<jats:sup>*<\/jats:sup>(U<jats:sub>P<\/jats:sub>\u2009\u2013\u2009U<jats:sub>R<\/jats:sub>)\/(ID<jats:sub>50<\/jats:sub>\u2009+\u2009D),<\/jats:styled-content> <jats:italic>r<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u00a0=\u00a00.60) did not include CL<jats:sub>CR<\/jats:sub> or diuretic use as covariates. There was no difference (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.87) between the predicted SU concentrations derived from the oxypurinol <jats:italic>concentration\u2013<\/jats:italic> and allopurinol <jats:italic>dose<\/jats:italic>\u2013response relationships. The nomogram constructed using the allopurinol <jats:italic>dose<\/jats:italic>\u2013response relationship for all recruited patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a081 patients) required pretreatment SU as the predictor of allopurinol maintenance dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Plasma oxypurinol concentrations, CL<jats:sub>CR<\/jats:sub> and diuretic status are not required to predict the maintenance dose of allopurinol. Using the nomogram, the maintenance dose of allopurinol estimated to reach target concentrations can be predicted from U<jats:sub>P<\/jats:sub>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13307","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T07:42:49Z","timestamp":1492501369000},"page":"2015-2026","source":"Crossref","is-referenced-by-count":20,"title":["Individualising the dose of allopurinol in patients with gout"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-7320","authenticated-orcid":false,"given":"Diluk R. 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