{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:44:59Z","timestamp":1787013899784,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T00:00:00Z","timestamp":1507593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Health and Care Research Wales \/ SRL\/15\/029"],"award-info":[{"award-number":["Health and Care Research Wales \/ SRL\/15\/029"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L004933\/1\u2010Q25"],"award-info":[{"award-number":["MR\/L004933\/1\u2010Q25"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Medical Research Council \/ MR\/K025635\/1"],"award-info":[{"award-number":["Medical Research Council \/ MR\/K025635\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Dual\u2010urate\u2010lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosuric agents can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of the present study were to simulate the relationship between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono\u2010 and dual\u2010ULTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The impact of poor medication adherence was studied using two\u2010compartment pharmacokinetic (PK) models based on published evidence, and a semi\u2010mechanistic four\u2010compartment pharmacodynamic (PD) model. The PKPD model was used to simulate mono and dual\u2010ULT in gout patients with either under\u2010excretion (lowered clearance) or overproduction of uric acid, with suboptimal adherence modelled as either a single drug holiday of increasing duration or doses taken at random.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Simulation results showed a surge in urinary uric acid occurring when dosing is restarted following missed doses. For under\u2010excreters taking a 20\u2010day drug holiday, the addition of 200\u00a0mg (or 400\u00a0mg) lesinurad to 80\u00a0mg febuxostat increased the percentage of patients experiencing hyperuricosuria from 0% to 1.4% (or 3.1%). In overproducers, restarting ULTs following drug holidays of more than 5\u00a0days leads to over 60% of patients experiencing hyperuricosuria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Suboptimal medication adherence may compromise the safety and efficacy of mono\u2010 and dual\u2010ULTs, especially in patients with gout resulting from an overproduction of uric acid. Clinicians and pharmacists should consider counselling patients with respect to the risks associated with partial adherence, and offer interventions to improve adherence or tailor treatments, where appropriate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.13427","type":"journal-article","created":{"date-parts":[[2017,9,9]],"date-time":"2017-09-09T17:22:36Z","timestamp":1504977756000},"page":"142-152","source":"Crossref","is-referenced-by-count":17,"title":["Impact of non\u2010adherence on the safety and efficacy of uric acid\u2010lowering therapies in the treatment of gout"],"prefix":"10.1111","volume":"84","author":[{"given":"Daniel","family":"Hill\u2010McManus","sequence":"first","affiliation":[{"name":"Centre for Health Economic and Medicines Evaluation Bangor University  Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Soto","sequence":"additional","affiliation":[{"name":"Pharmacometrics Pfizer Ltd  Sandwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Marshall","sequence":"additional","affiliation":[{"name":"Pharmacometrics Pfizer Ltd  Sandwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8247-7459","authenticated-orcid":false,"given":"Dyfrig","family":"Hughes","sequence":"additional","affiliation":[{"name":"Centre for Health Economic and Medicines Evaluation Bangor University  Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,10]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","article-title":"Gout","volume":"6736","author":"Dalbeth N","year":"2016","journal-title":"Lancet"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209707"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-1107-x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(02)01908-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-9140-5_46"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200403000-00006"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2016.09.006"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101115"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.5527\/wjn.v2.i2.17"},{"key":"e_1_2_7_11_1","unstructured":"EMA.Zurampic assessment report. vol. 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