{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T21:40:13Z","timestamp":1784670013715,"version":"3.55.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"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, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a parallel-group, open-label, single-dose clinical pharmacology study. Dotinurad (1\u00a0mg) was administered once, orally to subjects with mild (estimated glomerular filtration rate [eGFR],\u2009\u2265\u200960 to\u2009&lt;\u200990\u00a0mL\/min\/1.73 m<jats:sup>2<\/jats:sup>) or moderate (eGFR,\u2009\u2265\u200930 to\u2009&lt;\u200960\u00a0mL\/min\/1.73 m<jats:sup>2<\/jats:sup>) renal dysfunction or normal (eGFR,\u2009\u2265\u200990\u00a0mL\/min\/1.73 m<jats:sup>2<\/jats:sup>) renal function.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The time-course of mean plasma concentration of dotinurad had similar profiles across the groups. Regarding PK, there was no significant difference between the renal dysfunction groups and normal renal function group. Regarding PD, the maximum reduction rate in serum uric acid levels and the fractional uric acid excretion (FE) ratio (FE<jats:sub>0\u201324<\/jats:sub>\/FE<jats:sub>\u221224\u20130<\/jats:sub>) were significantly lower in the moderate renal dysfunction group than in the normal renal function group. However, other PD parameters were not significantly different among the groups. No notable adverse events or adverse drug reactions were observed in this study.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>These results suggested that no dose adjustment might be necessary when administering dotinurad to patients with mild-to-moderate renal dysfunction.<\/jats:p>\n<jats:p>ClinicalTrials.gov Identifier: NCT02347046.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s10157-019-01825-3","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T06:02:35Z","timestamp":1575957755000},"page":"17-24","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor"],"prefix":"10.1007","volume":"24","clinical-trial-number":[{"clinical-trial-number":"nct02347046","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Hiroyuki","family":"Fukase","sequence":"first","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":"Masahiko","family":"Fushimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Hosoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,10]]},"reference":[{"key":"1825_CR1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/art.1780150209","volume":"15","author":"JN Loeb","year":"1972","unstructured":"Loeb JN. The influence of temperature on the solubility of monosodium urate. Arthritis Rheum. 1972;15:189\u201392.","journal-title":"Arthritis Rheum."},{"key":"1825_CR2","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/0002-9343(65)90048-3","volume":"39","author":"WN Mikkelsen","year":"1965","unstructured":"Mikkelsen WN, Valkenburg H. The distribution of serum uric acid values in a population unselected as to gout or hyperuricemia. Am J Med. 1965;39:242\u201351.","journal-title":"Am J Med."},{"key":"1825_CR3","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1681\/ASN.2007101075","volume":"19","author":"DE Weiner","year":"2008","unstructured":"Weiner DE, Tighiouart H, Elsayed EF, et al. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008;19:1204\u201311.","journal-title":"J Am Soc Nephrol."},{"key":"1825_CR4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.2188\/jea.10.403","volume":"10","author":"M Tomita","year":"2000","unstructured":"Tomita M, Mizuno S, Murayama T, et al. Dose hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. I Epidemiol. 2000;10:403\u20139.","journal-title":"I Epidemiol."},{"key":"1825_CR5","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1056\/NEJM197906283002604","volume":"300","author":"GR Boss","year":"1979","unstructured":"Boss GR, Seegmiller JE. Hyperuricemia and gout; classification, complications and management. N Engl J Med. 1979;300:1459\u201368.","journal-title":"N Engl J Med."},{"key":"1825_CR6","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1002\/art.20102","volume":"50","author":"TR Mikuls","year":"2004","unstructured":"Mikuls TR, MacLean CH, Olivieri J, et al. Quality of care indicators for gout management. Arthritis Rheum. 2004;50:937\u201343.","journal-title":"Arthritis Rheum."},{"key":"1825_CR7","unstructured":"Japanese Society of Gout and Uric & Nucleic Acids: guideline for the management of hyperuricemia and gout: 2nd edition. 2010."},{"issue":"10","key":"1825_CR8","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.2147\/DDDT.S119944","volume":"1","author":"M Gillen","year":"2016","unstructured":"Gillen M, Valdez S, Shen Z, et al. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers. Drug Des Devel Ther. 2016;1(10):3555\u2013622.","journal-title":"Drug Des Devel Ther."},{"key":"1825_CR9","doi-asserted-by":"publisher","first-page":"643","DOI":"10.2165\/00002018-200831080-00002","volume":"31","author":"MH Lee","year":"2008","unstructured":"Lee MH, Graham GG, Day RO, et al. A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients? Drug Saf. 2008;31:643\u201365.","journal-title":"Drug Saf."},{"key":"1825_CR10","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1053\/j.ajkd.2007.05.013","volume":"50","author":"M Chonchol","year":"2007","unstructured":"Chonchol M, Shlipak MG, Fried LF, et al. Relationship of uric acid with progression of kidney disease. Am J Kidney Dis. 2007;50:239\u201347.","journal-title":"Am J Kidney Dis."}],"container-title":["Clinical and Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01825-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10157-019-01825-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-019-01825-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T14:22:42Z","timestamp":1628605362000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10157-019-01825-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,10]]},"references-count":10,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["1825"],"URL":"https:\/\/doi.org\/10.1007\/s10157-019-01825-3","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,10]]},"assertion":[{"value":"1 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 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 an advisor to Fuji regarding this study and received consultant and manuscript fees. HF was principal investigator to this study and received 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 (CPC Clinical Trial Hospital; Kagoshima, 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 requirements by regulation. The information in this study was registered with Clinical Trials.gov (ClinicalTrials.gov number: NCT02347046).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}