{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:09:28Z","timestamp":1788206968474,"version":"build-2803163510"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,10,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Loop diuretics are highly natriuretic but their short duration of action permits postdiuretic sodium retention, which limits salt loss unless dietary salt is severely restricted. We tested the hypothesis that a more prolonged duration of action would enhance salt loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Ten healthy participants were crossed over between 20\u00a0mg of oral immediate\u2010release or extended\u2010release (\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      ) torsemide while consuming a fixed diet with 300\u00a0mmol\u00b7d\n                      <jats:sup>\u22121<\/jats:sup>\n                      of Na\n                      <jats:sup>+<\/jats:sup>\n                      . Compared with immediate\u2010release, plasma torsemide after\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      was 59% lower at 1 to 3\u00a0hours but 97% higher at 8 to 10\u00a0hours as a result of a &gt;3\u2010fold prolongation of time to maximal plasma concentrations. The relationship of natriuresis to log torsemide excretion showed marked hysteresis, but participants spent twice as long with effective concentrations of torsemide after\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      , thereby enhancing diuretic efficiency. Compared with immediate\u2010release,\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      torsemide did not reduce creatinine clearance and increased fluid (1634\u00b1385 versus 728\u00b1445\u00a0mL,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.02) and Na\n                      <jats:sup>+<\/jats:sup>\n                      output (98\u00b115 versus 42\u00b117\u00a0mmol,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05) despite an 18% reduction in exposure. Neither formulation increased K\n                      <jats:sup>+<\/jats:sup>\n                      excretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Torsemide\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      prolongs urine drug levels, thereby increasing the time spent with effective drug concentrations, reduces postdiuretic Na\n                      <jats:sup>+<\/jats:sup>\n                      retention, and moderates a fall in glomerular filtration rate. It caused significant Na\n                      <jats:sup>+<\/jats:sup>\n                      loss even during very high salt intake. Thus, a short duration of action limits salt loss with loop diuretics. These conclusions warrant testing in subjects with edema and heart failure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.117.006135","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T20:10:26Z","timestamp":1507234226000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Sodium and Fluid Excretion With Torsemide in Healthy Subjects is Limited by the Short Duration of Diuretic Action"],"prefix":"10.1161","volume":"6","author":[{"given":"Salim","family":"Shah","sequence":"first","affiliation":[{"name":"Sarfez Pharmaceuticals, Inc., McLean, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Michigan, Ann Arbor, MI"},{"name":"Sarfez Pharmaceuticals, Inc., McLean, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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