{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:37:10Z","timestamp":1761917830110,"version":"build-2065373602"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T00:00:00Z","timestamp":1485475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      The selective endothelin (\n                      <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\n                      ) A receptor antagonist atrasentan has been shown to lower albuminuria in\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      merican and\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sian patients with type 2 diabetes and nephropathy. As drug responses to many drugs may differ between\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      merican and\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sian populations, we assessed the influence of geographical region on the albuminuria and fluid retention response to atrasentan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Two 12\u2010week double\u2010blind randomised controlled trials were performed with atrasentan 0.75 or 1.25\u2009mg\/d vs placebo in patients with type 2 diabetes and nephropathy. The efficacy endpoint was the percentage change in albuminuria. Bodyweight change, a proxy of fluid retention, was used as a safety endpoint. Pharmacodynamics were determined in\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sians (\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      \u2009=\u200977) and\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      mericans (\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      \u2009=\u2009134). Atrasentan plasma concentration was measured in 161 atrasentan\u2010treated patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean albuminuria reduction in Asian, compared to\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      merican, patients was, respectively, \u221234.4% vs \u221226.3% for 0.75\u2009mg\/d (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2009=\u2009.44) and \u221248.0% vs \u221228.9% for 1.25\u2009mg\/d (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2009=\u2009.035). Bodyweight gain did not differ between\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      merican and\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sian populations. Atrasentan plasma concentrations were higher in\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sians compared to\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      mericans and correlated with albuminuria response (7.2% albuminuria reduction per doubling atrasentan concentration;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2009=\u2009.024). Body surface area (\u03b2\u2009=\u2009\u22121.09 per m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2009&lt;\u2009.001) and bilirubin, as a marker of hepatic organic anion transporter activity, (\u03b2\u2009=\u20090.69 per mg\/\n                      <jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>\n                      increment;\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:styled-content>\n                      \u2009=\u2009.010) were independent determinants of atrasentan plasma concentration; correction by body surface area and bilirubin left no significant difference in plasma concentration between\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sian and\n                      <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\n                      orth\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      merican populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The higher exposure and albuminuria reduction of atrasentan in\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sian patients is not associated with more fluid retention, suggesting that\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      sian patients are less sensitive to atrasentan\u2010induced sodium retention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12851","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T07:50:24Z","timestamp":1481961024000},"page":"545-552","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of exposure response relationship of atrasentan between\n                    <scp>N<\/scp>\n                    orth\n                    <scp>A<\/scp>\n                    merican and\n                    <scp>A<\/scp>\n                    sian populations"],"prefix":"10.1111","volume":"19","author":[{"given":"Hiddo J. L.","family":"Heerspink","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Makino","sequence":"additional","affiliation":[{"name":"Okayama University Graduate School of Medicine  Okayama City Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Andress","sequence":"additional","affiliation":[{"name":"Renal Clinical Development AbbVie  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Renal Clinical Development AbbVie  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Correa\u2010Rotter","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute Salvador Zubir\u00e1n  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blai","family":"Coll","sequence":"additional","affiliation":[{"name":"Renal Clinical Development AbbVie  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin W.","family":"Davis","sequence":"additional","affiliation":[{"name":"Renal Clinical Development AbbVie  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Idler","sequence":"additional","affiliation":[{"name":"Renal Clinical Development AbbVie  Chicago Illinois"}],"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan","family":"Liu","sequence":"additional","affiliation":[{"name":"Renal Clinical Development AbbVie  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"George Institute for Global Health University of Sydney  Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Remuzzi","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera Papa Giovanni XXIII and IRCCS\u2010Istituto di Ricerche Farmacologiche Mario Negri  Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheldon W.","family":"Tobe","sequence":"additional","affiliation":[{"name":"Department of Hypertension and Nephrology, Sunnybrook Health Sciences Centre  Toronto Ontario 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