{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:49:56Z","timestamp":1786992596134,"version":"build-2736575974"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Dotinurad is a novel selective urate reabsorption inhibitor (SURI) which reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). This study was intended to verify the efficacy and safety of dotinurad following treatment for 34 or 58\u00a0weeks in hyperuricemic patients with or without gout.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>This long-term study had an open-label design with dose escalation. The dose of dotinurad started at 0.5\u00a0mg\/day and was increased progressively to 2\u00a0mg\/day. If the serum uric acid level of patients did not reach\u2009\u2264\u20096\u00a0mg\/dL at week 14, the dose was increased to 4\u00a0mg\/day. The primary endpoint was the percent change in serum uric acid level from the baseline to each visit.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>At a dose of 2\u00a0mg, serum uric acid levels at week 34 and 58 were reduced from the baseline by 46.73% and 47.17%, respectively; at 4\u00a0mg, the respective values were 54.92% and 57.35%. At week 34 and 58, the percentages of patients achieving a serum uric acid levels\u2009\u2264\u20096.0\u00a0mg\/dL with 2-mg dose were 89.11% and 91.30%, respectively; with 4\u00a0mg, the respective rates were 97.50% and 100.00%. In addition, the incidences of adverse events and adverse drug reactions were 65.2% and 21.8%, respectively.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Dotinurad at doses of 2\u20134-mg sufficiently reduced serum uric acid levels in hyperuricemic patients with or without gout, and its efficacy and safety were verified for long-term administration.<\/jats:p>\n<jats:p>ClinicalTrials.gov Identifier: NCT03006445<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s10157-019-01831-5","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T03:02:20Z","timestamp":1577329340000},"page":"80-91","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Open-label study of long-term administration of dotinurad in Japanese hyperuricemic patients with or without gout"],"prefix":"10.1007","volume":"24","author":[{"given":"Tatsuo","family":"Hosoya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Fushimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Okui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomitsu","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"1831_CR1","unstructured":"Japanese Society of Gout and Nucleic Acid Metabolism. Guideline for the management of hyperuricemia and gout. 3rd edition. Tokyo; 2018."},{"key":"1831_CR2","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/S0272-6386(04)00934-5","volume":"44","author":"K Iseki","year":"2004","unstructured":"Iseki K, Ikemiya Y, Inoue T, et al. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44:642\u201350.","journal-title":"Am J Kidney Dis."},{"key":"1831_CR3","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/hr.2013.11","volume":"36","author":"K Iseki","year":"2013","unstructured":"Iseki K, Iseki C, Kinjo K. Changes in serum uric acid have a reciprocal effect on eGFR change: a 10-year follow-up study of community-based screening in Okinawa. Japan. Hypertens Res. 2013;36:650\u20134.","journal-title":"Japan. Hypertens Res."},{"key":"1831_CR4","doi-asserted-by":"publisher","first-page":"4002","DOI":"10.1002\/art.30649","volume":"63","author":"F Perez-Ruiz","year":"2011","unstructured":"Perez-Ruiz F, Herrero-Beites AM, Carmona L. A two-stage approach to the treatment of hyperuricemia in gout: the dirty dish hypothesis. Arthritis Rheum. 2011;63:4002\u20136.","journal-title":"Arthritis Rheum."},{"key":"1831_CR5","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1093\/rheumatology\/kex350","volume":"56","author":"AK Tausche","year":"2017","unstructured":"Tausche AK, Alten R, Dalbeth N, et al. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study. Rheumatology. 2017;56:2170\u20138.","journal-title":"Rheumatology"},{"key":"1831_CR6","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1124\/jpet.119.259341","volume":"371","author":"T Taniguchi","year":"2019","unstructured":"Taniguchi T, Ashizawa N, Matsumoto K, et al. Pharmacological evaluation of dotinurad, a selective urate reabsorption inhibitor. J Pharmacol Exp Ther. 2019;371:162\u201370.","journal-title":"J Pharmacol Exp Ther."},{"key":"1831_CR7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/978-1-4615-5381-6_3","volume":"431","author":"H Yamanaka","year":"1998","unstructured":"Yamanaka H, Togashi R, Hakoda M, et al. Optimal range of serum urate concentrations to minimize risk of gouty attacks during anti-hyperuricemic treatment. Adv Exp Med Biol. 1998;431:13\u20138.","journal-title":"Adv Exp Med Biol."},{"key":"1831_CR8","doi-asserted-by":"crossref","unstructured":"Yamanaka H, Japanese Society of Gout and Nucleic Acid Metabolism. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids. 2011; 30: 1018\u201329.","DOI":"10.1080\/15257770.2011.596496"},{"key":"1831_CR9","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1007\/s10157-014-0935-8","volume":"18","author":"T Hosoya","year":"2014","unstructured":"Hosoya T, Ohno I, Nomura S, et al. Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clin Exp Nephrol. 2014;18:876\u201384.","journal-title":"Clin Exp Nephrol."},{"key":"1831_CR10","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1053\/j.ajkd.2015.05.017","volume":"66","author":"D Sircar","year":"2015","unstructured":"Sircar D, Chatterjee S, Waikhom R, et al. Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic,Hyperuricemia: A 6-Month, Double-Blind, Randomized,Placebo-Controlled Trial. Am J Kidney Dis. 2015;66:945\u201350.","journal-title":"Am J Kidney Dis."},{"key":"1831_CR11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1002\/art.39840","volume":"69","author":"KG Saag","year":"2017","unstructured":"Saag KG, Fitz-Patrick D, Kopicko J, et al. Lesinurad Combined with allopurinol: a randomized, double-blind, placebo-controlled study in gout patients with an inadequate response to standard-of-care allopurinol (a US-based study). Arthritis Rheumatol. 2017;69:203\u201312.","journal-title":"Arthritis Rheumatol."},{"key":"1831_CR12","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1002\/art.40159","volume":"69","author":"N Dalbeth","year":"2017","unstructured":"Dalbeth N, Jones G, Terkeltaub R, et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: findings of a phase III clinical trial. Arthritis Rheumatol. 2017;69:1903\u201313.","journal-title":"Arthritis Rheumatol."}],"container-title":["Clinical and Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01831-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10157-019-01831-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01831-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T00:09:38Z","timestamp":1608854978000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10157-019-01831-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":12,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["1831"],"URL":"https:\/\/doi.org\/10.1007\/s10157-019-01831-5","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]},"assertion":[{"value":"2 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Fuji Yakuhin Co., Ltd. (Fuji), the manufacturer of dotinurad, sponsored this study. TH was advisor to Fuji regarding this study and received consultant and manuscript fees. The other authors were employees of Fuji.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study protocol and informed consent document were reviewed and approved by an institutional review board (Shinagawa East One Medical Clinic, Tokyo, Japan; Tokyo University Hospital, Tokyo, Japan; Kyoto University Hospital, Kyoto, Japan). Informed consent was obtained from all individual participants included in the study. The tests were conducted in compliance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, Good Clinical Practice guidelines, and other regulatory requirements that were relevant. The information in this study was registered with Clinical Trials.gov (ClinicalTrials.gov number: NCT03006445).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}