{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:04:13Z","timestamp":1787313853827,"version":"build-2736575974"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2774,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T00:00:00Z","timestamp":1526515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Birmingham Racing Commission"},{"name":"The Department of Clinical Sciences at Auburn University"},{"name":"Birmingham Racing Commission"},{"name":"The Department of Clinical Sciences at Auburn University"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Six healthy adult mares.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg\/kg PO) and pharmacodynamic effects of long-term torsemide administration (2 mg\/kg PO q12h) for 6 days in healthy horses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pharmacokinetic analysis identified a peak concentration (Cmax) of 10.14 \u00b5g\/mL (range, 6.79\u201314.69 \u00b5g\/mL) and elimination half-life (T1\/2) 9.2 hours (range, 8.4\u201310.4 hours). The area under the plasma drug concentration over time curve (AUC) was 80.7 \u00b5g \u00d7 h\/mL (range, 56.5\u2013117.2 \u00b5g \u00d7 h\/mL). A statistically significant increase in urine volume and decrease in urine specific gravity were found from day 0 (baseline) to day 6 (P\u2009&amp;lt;\u2009.0001). Significant alterations in biochemical variables included hyponatremia, hypokalemia, hypochloremia, and increased serum creatinine concentration. Mean arterial blood pressure significantly decreased on day 6 (57.7\u2009\u00b1\u20098.8 mm Hg, P\u2009=\u2009.001) as compared with baseline (78\u2009\u00b1\u20096.1 mm Hg). Serum aldosterone concentrations significantly increased after 6 days of torsemide administration (P\u2009=\u2009.0006).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>PO administered torsemide (4 mg\/kg\/day) successfully reached therapeutic concentrations in blood, induced clinically relevant diuresis, and resulted in moderate pre-renal azotemia and electrolyte disturbances.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.15213","type":"journal-article","created":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T05:50:58Z","timestamp":1526536258000},"page":"1428-1435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses"],"prefix":"10.1093","volume":"32","author":[{"given":"Gustavo F.","family":"Agne","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Auburn University Department of Clinical Sciences, ,Auburn, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-3084","authenticated-orcid":false,"given":"Seung Woo","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Auburn University Department of Clinical Sciences, ,Auburn, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne A.","family":"Wooldridge","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Auburn University Department of Clinical Sciences, ,Auburn, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan H.","family":"Duran","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Auburn University Department of Clinical Sciences, ,Auburn, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Ravis","sequence":"additional","affiliation":[{"name":"Harrison School of Pharmacy, Auburn University Department of Drug Discovery and Development, ,Auburn, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro","family":"Toribio","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, The Ohio State University Department of Clinical Sciences, ,Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,1]]},"reference":[{"key":"2026020303310485700_jvim15213-bib-0001","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1939-1676.2004.tb02614.x","article-title":"Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses","volume":"18","author":"Johansson","year":"2004","journal-title":"J Vet Intern Med."},{"key":"2026020303310485700_jvim15213-bib-0002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00003088-199834010-00001","article-title":"Clinical pharmacokinetics and pharmacodynamics of torasemide","volume":"34","author":"Knauf","year":"1998","journal-title":"Clin Pharmacokinet."},{"key":"2026020303310485700_jvim15213-bib-0003","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/clpt.1980.111","article-title":"Renal tubular secretion and effects of furosemide","volume":"27","author":"Odlind","year":"1980","journal-title":"Clin Pharmacol Ther."},{"key":"2026020303310485700_jvim15213-bib-0004","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/jvim.12043","article-title":"Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals","volume":"27","author":"Dembek","year":"2013","journal-title":"J Vet Intern Med."},{"key":"2026020303310485700_jvim15213-bib-0005","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.2042-3306.1995.tb04995.x","article-title":"The pharmacological basis of cardiac drug selection for use in horses","volume":"27","author":"Baggot","year":"2010","journal-title":"Equine Vet J."},{"key":"2026020303310485700_jvim15213-bib-0006","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.2147\/DDDT.S86300","article-title":"Randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of torasemide-PR 10 mg, torasemide-IR 10 mg, and furosemide-IR 40 mg, in patients with chronic heart failure","volume":"9","author":"Ballester","year":"2015","journal-title":"Drug Des Devel Ther."},{"key":"2026020303310485700_jvim15213-bib-0007","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJM199808063390607","article-title":"Diuretic therapy","volume":"339","author":"Brater","year":"1998","journal-title":"N Engl J Med."},{"key":"2026020303310485700_jvim15213-bib-0008","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jvc.2012.01.003","article-title":"Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease","volume":"14","author":"Peddle","year":"2012","journal-title":"J Vet Cardiol."},{"key":"2026020303310485700_jvim15213-bib-0009","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.2042-3306.1997.tb03127.x","article-title":"Pulmonary vascular pressures of strenuously exercising Thoroughbreds after administration of varying doses of frusemide","volume":"29","author":"Manohar","year":"1997","journal-title":"Equine Vet J."},{"key":"2026020303310485700_jvim15213-bib-0010","first-page":"29","article-title":"Torasemide dose-proportionality of pharmacokinetics and pharmacodynamics","volume":"8","author":"Barr","year":"1990","journal-title":"Prog Pharmacol Clin Pharmacol."},{"key":"2026020303310485700_jvim15213-bib-0011","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/jvp.12316","article-title":"A pharmacokinetic\/pharmacodynamic model capturing the time course of torasemide-induced diuresis in the dog","volume":"39","author":"Paulin","year":"2016","journal-title":"J Vet Pharmacol Ther."},{"key":"2026020303310485700_jvim15213-bib-0012","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1292\/jvms.65.1057","article-title":"The effects of the loop diuretics furosemide and torasemide on diuresis in dogs and cats","volume":"65","author":"Uechi","year":"2003","journal-title":"J Vet Med Sci."},{"key":"2026020303310485700_jvim15213-bib-0013","first-page":"1520","article-title":"Pharmacological properties of the new potent diuretic torasemide in rats and dogs","volume":"35","author":"Ghys","year":"1985","journal-title":"Arzneimittelforschung."},{"key":"2026020303310485700_jvim15213-bib-0014","first-page":"29","article-title":"Accidental intracarotid artery injection of promazine in the horse","volume":"15","author":"Christian","year":"1974","journal-title":"Can Vet J."},{"key":"2026020303310485700_jvim15213-bib-0015","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/0009-9236(95)90222-8","article-title":"Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure","volume":"57","author":"Vargo","year":"1995","journal-title":"Clin Pharmacol Ther."},{"key":"2026020303310485700_jvim15213-bib-0016","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF00315407","article-title":"Pharmacokinetics of torasemide and its metabolites in healthy controls and in chronic renal failure","volume":"39","author":"Spahn","year":"1990","journal-title":"Eur J Clin Pharmacol."},{"key":"2026020303310485700_jvim15213-bib-0017","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/0016-6480(82)90140-X","article-title":"Dynamics of renin and aldosterone in the thoroughbred horse","volume":"48","author":"Guthrie","year":"1982","journal-title":"Gen Comp Endocrinol."},{"key":"2026020303310485700_jvim15213-bib-0018","doi-asserted-by":"crossref","first-page":"e73737","DOI":"10.1371\/journal.pone.0073737","article-title":"The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes","volume":"8","author":"Gravez","year":"2013","journal-title":"PLoS One."},{"key":"2026020303310485700_jvim15213-bib-0019","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.2460\/ajvr.68.10.1058","article-title":"Effects of oral administration of furosemide and torsemide in healthy dogs","volume":"68","author":"Hori","year":"2007","journal-title":"Am J Vet Res."},{"key":"2026020303310485700_jvim15213-bib-0020","doi-asserted-by":"crossref","first-page":"519","DOI":"10.4103\/0250-474X.44609","article-title":"A simplified HPLC method for quantification of torsemide from human plasma and its application to a bioequivalence study","volume":"70","author":"Khan","year":"2008","journal-title":"Indian J Pharm Sci."},{"key":"2026020303310485700_jvim15213-bib-0021","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/jvim.13928","article-title":"Accuracy and precision of noninvasive blood pressure in normo-, hyper-, and hypotensive standing and anesthetized adult horses","volume":"30","author":"Heliczer","year":"2016","journal-title":"J Vet Intern Med."},{"key":"2026020303310485700_jvim15213-bib-0022","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.2042-3306.1992.tb02820.x","article-title":"Standardised imaging technique for guided M-mode and Doppler echocardiography in the horse","volume":"24","author":"Long","year":"1992","journal-title":"Equine Vet J."},{"key":"2026020303310485700_jvim15213-bib-0023","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/jvim.12034","article-title":"Doppler and volumetric echocardiographic methods for cardiac output measurement in standing adult horses","volume":"27","author":"McConachie","year":"2013","journal-title":"J Vet Intern Med."},{"key":"2026020303310485700_jvim15213-bib-0024","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/jvim.13800","article-title":"Atrial fibrillation as a prognostic indicator in medium to large-sized dogs with myxomatous mitral valvular degeneration and congestive heart failure","volume":"30","author":"Jung","year":"2016","journal-title":"J Vet Intern Med."},{"key":"2026020303310485700_jvim15213-bib-0025","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.2042-3306.2010.00244.x","article-title":"Plasma aldosterone concentration and cardiovascular response to low sodium intake in horses in training","volume":"42","author":"Jansson","year":"2010","journal-title":"Equine Vet J."},{"key":"2026020303310485700_jvim15213-bib-0026","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.2042-3306.2010.00211.x","article-title":"Dehydration, electrolyte imbalances and renin-angiotensin-aldosterone-vasopressin axis in successful and unsuccessful endurance horses","volume":"42","author":"Munoz","year":"2010","journal-title":"Equine Vet J."},{"key":"2026020303310485700_jvim15213-bib-0027","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/bdd.401","article-title":"Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits","volume":"25","author":"Kim","year":"2004","journal-title":"Biopharm Drug Dispos."},{"key":"2026020303310485700_jvim15213-bib-0028","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s004670050796","article-title":"Torasemide is an effective diuretic in the newborn rabbit","volume":"14","author":"Dubourg","year":"2000","journal-title":"Pediatr Nephrol."},{"key":"2026020303310485700_jvim15213-bib-0029","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/00045391-199506000-00010","article-title":"Effect of food on the pharmacokinetics and pharmacodynamics of torsemide","volume":"2","author":"Kramer","year":"1995","journal-title":"Am J Ther."},{"key":"2026020303310485700_jvim15213-bib-0030","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1527-5299.2003.02399.x","article-title":"Drug absorption in the management of congestive heart failure: loop diuretics","volume":"9","author":"Sica","year":"2003","journal-title":"Congest Heart Fail."},{"key":"2026020303310485700_jvim15213-bib-0031","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF00541464","article-title":"Torasemide, a new potent diuretic. Double-blind comparison with furosemide","volume":"31","author":"Broekhuysen","year":"1986","journal-title":"Eur J Clin Pharmacol."},{"key":"2026020303310485700_jvim15213-bib-0032","doi-asserted-by":"crossref","first-page":"PL45","DOI":"10.1016\/S0024-3205(98)00265-3","article-title":"Torsemide inhibits aldosterone secretion in vitro","volume":"63","author":"Goodfriend","year":"1998","journal-title":"Life Sci."},{"key":"2026020303310485700_jvim15213-bib-0033","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0014-2999(91)90812-5","article-title":"Anti-aldosteronergic effect of torasemide","volume":"205","author":"Uchida","year":"1991","journal-title":"Eur J Pharmacol."},{"key":"2026020303310485700_jvim15213-bib-0034","first-page":"76","article-title":"The Equine Fluid Therapy","author":"Stewart","year":"2014"},{"key":"2026020303310485700_jvim15213-bib-0035","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cveq.2014.11.011","article-title":"Update on exercise-induced pulmonary hemorrhage","volume":"31","author":"Sullivan","year":"2015","journal-title":"Vet Clin North Am Equine Pract."},{"key":"2026020303310485700_jvim15213-bib-0036","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S0002-9343(01)00903-2","article-title":"Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure","volume":"111","author":"Murray","year":"2001","journal-title":"Am J Med."},{"key":"2026020303310485700_jvim15213-bib-0037","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1248\/yakushi.129.871","article-title":"Effects of various diuretics on cardiac function in rats with heart failure","volume":"129","author":"Tanaka","year":"2009","journal-title":"Yakugaku Zasshi."},{"key":"2026020303310485700_jvim15213-bib-0038","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1136\/vr.160.24.847","article-title":"Effect of torsemide on serum and urine electrolyte levels in dogs with congestive heart failure","volume":"160","author":"Caro-Vadillo","year":"2007","journal-title":"Vet Rec."},{"key":"2026020303310485700_jvim15213-bib-0039","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/jvim.12153","article-title":"Pharmacodynamic evaluation of 4 angiotensin-converting enzyme inhibitors in healthy adult horses","volume":"27","author":"Afonso","year":"2013","journal-title":"J Vet Intern Med."},{"key":"2026020303310485700_jvim15213-bib-0040","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.cveq.2016.11.005","article-title":"Equine cardiovascular therapeutics","volume":"33","author":"Sleeper","year":"2017","journal-title":"Vet Clin North Am Equine Pract."}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvim.15213","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/32\/4\/1428\/66671034\/jvim15213.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/32\/4\/1428\/66671034\/jvim15213.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:31:14Z","timestamp":1770107474000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/32\/4\/1428\/8449745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,1]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,7,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.15213","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,7]]},"published":{"date-parts":[[2018,7,1]]},"assertion":[{"value":"2017-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}