{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T16:32:18Z","timestamp":1770568338694,"version":"3.49.0"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["OC0013659"],"award-info":[{"award-number":["OC0013659"]}],"id":[{"id":"10.13039\/501100009708","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\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long\u2010term outcomes for kidney protection and heart failure in the phase III SONAR trial (<jats:italic>n\u00a0<\/jats:italic>=\u00a03668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75\u00a0mg\/day. Parametric time\u2010to\u2010event models were used to quantify the association between plasma exposure and long\u2010term outcomes. Mean atrasentan plasma exposure was 41.4\u00a0ng.h\/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28\u20130.85) for kidney events and 1.13 (95% CI: 1.03\u20132.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75\u00a0mg\/day dose in this population.<\/jats:p>","DOI":"10.1002\/cpt.2143","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T21:43:26Z","timestamp":1608327806000},"page":"1631-1638","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Individual Atrasentan Exposure is Associated With Long\u2010term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease"],"prefix":"10.1111","volume":"109","author":[{"given":"Jeroen V.","family":"Koomen","sequence":"first","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasper","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Bakris","sequence":"additional","affiliation":[{"name":"American Society of Hypertension Comprehensive Hypertension Center University of Chicago Medicine and Biological Sciences Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Correa\u2010Rotter","sequence":"additional","affiliation":[{"name":"National Medical Science and Nutrition Institute Salvador Zubir\u00e1n Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan Fan","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Nephrology Nanfang Hospital Southern Medical University National Clinical Research Center for Kidney Disease Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalane W.","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald E.","family":"Kohan","sequence":"additional","affiliation":[{"name":"Division of Nephrology University of Utah Health Sciences Center Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Makino","sequence":"additional","affiliation":[{"name":"Okayama University Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J. V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre University of Glasgow Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"George Institute for Global Health and University of New South Wales Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheldon W.","family":"Tobe","sequence":"additional","affiliation":[{"name":"Division of Nephrology Sunnybrook Health Sciences Centre University of Toronto and the Northern Ontario School of Medicine Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiddo J. 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