{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:23:19Z","timestamp":1780417399546,"version":"3.54.1"},"reference-count":12,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["917.15.306"],"award-info":[{"award-number":["917.15.306"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF14SA0003"],"award-info":[{"award-number":["NNF14SA0003"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n                    This study aimed to identify the optimal dose of the endothelin\u20101 receptor antagonist atrasentan with maximal albuminuria reduction and minimal signs of sodium retention, as manifested by increase in bodyweight. Data from the RADAR\u2010JAPAN studies were used, evaluating the effect of 0.75 or 1.25\u2009mg\/d of atrasentan in 161 patients with type 2 diabetes and kidney disease. Individual pharmacokinetic parameters were estimated using a population pharmacokinetic approach. Subsequently, changes in the urinary albumin\u2010to\u2010creatinine ratio (UACR) and bodyweight from baseline after 2\u2009weeks' exposure were modelled as a function of the pharmacokinetic parameters. The 0.75 and 1.25\u2009mg doses showed a mean UACR reduction of 34.0% and 40.1%, whereas mean bodyweight increased by 0.9 and 1.1\u2009kg, respectively. A large variation between individuals was observed in the UACR and bodyweight responses. Individual pharmacokinetic parameters correlated significantly with both individual UACR and bodyweight responses (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009.01). The individual response curves for UACR and bodyweight crossed at approximately the mean trough concentration of 0.75\u2009mg atrasentan, indicating that 0.75\u2009mg\/d of atrasentan is the optimal dose for kidney protection with maximal efficacy (albuminuria reduction) and safety (minimal sodium retention).\n                  <\/jats:p>","DOI":"10.1111\/dom.13312","type":"journal-article","created":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T06:46:05Z","timestamp":1522478765000},"page":"2019-2022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Determining the optimal dose of atrasentan by evaluating the exposure\u2010response relationships of albuminuria and bodyweight"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7253-3998","authenticated-orcid":false,"given":"Jeroen V.","family":"Koomen","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-9008","authenticated-orcid":false,"given":"Jasper","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nael M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Research and Development  AbbVie, North Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Henrik","family":"Parving","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology Rigshospitalet, University of Copenhagen  Copenhagen Denmark"},{"name":"Faculty of Health Science Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13245"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.02.019"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009060593"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13315"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013080830"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2017.07.011"},{"key":"e_1_2_6_8_1","volume-title":"ICH Topic E 4: Dose Response Information to Support Drug Registration","author":"European Medicines Agency","year":"1994"},{"key":"e_1_2_6_9_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration. Guidance for Industry: Exposure\u2010Response relationships \u2010 Study Design Data Analysis and Regulatory Applications. Rockville MD United States;2003."},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv210"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00613.2012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.15"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008050482"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13312","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T04:57:44Z","timestamp":1761886664000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":12,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1111\/dom.13312"],"URL":"https:\/\/doi.org\/10.1111\/dom.13312","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"2018-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}