{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:54:18Z","timestamp":1778648058074,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T00:00:00Z","timestamp":1462924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>Congestive heart failure (<jats:styled-content style=\"fixed-case\">CHF<\/jats:styled-content>) is a leading cause of mortality with an increasing prevalence in human and canine populations. While furosemide is a loop diuretic prescribed for the majority of<jats:styled-content style=\"fixed-case\">CHF<\/jats:styled-content>patients to reduce fluid retention, it also activates the renin\u2013angiotensin aldosterone system (<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>) which further contributes to the accelerated progression of heart failure. Our objective was to quantify the effect of furosemide on diuresis, renin activity (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>), and aldosterone (<jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>) in dogs, using a combined multiple comparisons and model\u2010based approach (<jats:styled-content style=\"fixed-case\">MCP<\/jats:styled-content>\u2010Mod). Twenty\u2010four healthy beagle dogs were allocated to four treatment groups (saline vs. furosemide 1, 2, and 4\u00a0mg\/kg i.m., q12\u00a0h for 5\u00a0days). Data from<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>values at furosemide trough concentrations, as well as 24\u2010h Diuresis, were analyzed using the<jats:styled-content style=\"fixed-case\">MCP<\/jats:styled-content>\u2010Mod procedure. A combination of E<jats:sub>max<\/jats:sub>models adequately described the dose\u2013response relationships of furosemide for the various endpoints. The dose\u2013response curves of<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>were found to be well in agreement, with an apparent shallower slope compared with 24\u2010h Diuresis. The research presented herein constitutes the first application of<jats:styled-content style=\"fixed-case\">MCP<\/jats:styled-content>\u2010Mod in Veterinary Medicine. Our data show that furosemide produces a submaximal effect on diuresis at doses lower than those identified to activate the circulating<jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jvp.12313","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T05:39:29Z","timestamp":1462945169000},"page":"539-546","source":"Crossref","is-referenced-by-count":7,"title":["Multiple comparison procedure and modeling: a versatile tool for evaluating dose\u2013response relationships in veterinary pharmacology \u2013 a case study with furosemide"],"prefix":"10.1111","volume":"39","author":[{"given":"B.","family":"Bieth","sequence":"first","affiliation":[{"name":"Department of Pharmacometrics, Biostatistical Sciences &amp; Pharmacometrics Novartis Pharma AG Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Bornkamp","sequence":"additional","affiliation":[{"name":"Statistical Methodology, Biostatistical Sciences &amp; Pharmacometrics Novartis Pharma AG Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Toutain","sequence":"additional","affiliation":[{"name":"Companion Animal Development Novartis Animal Health Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Garcia","sequence":"additional","affiliation":[{"name":"New Product Development Novartis Animal Health US, Inc. Greensboro NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. P.","family":"Mochel","sequence":"additional","affiliation":[{"name":"Department of Pharmacometrics, Biostatistical Sciences &amp; Pharmacometrics Novartis Pharma AG Basel Switzerland"},{"name":"Department of Pharmacology Leiden\u2010Academic Centre for Drug Research Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,5,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2009.0392.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvc.2012.01.011"},{"key":"e_1_2_7_4_1","first-page":"193","volume-title":"Modern Approaches to Clinical Trials Using SAS: Classical, Adaptive, and Bayesian Methods","author":"Bornkamp B.","year":"2015"},{"key":"e_1_2_7_5_1","unstructured":"Bornkamp B. 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