{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:23:33Z","timestamp":1777530213369,"version":"3.51.4"},"reference-count":19,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:p>\n                    Background: Tolvaptan, a nonpeptide selective vasopressin receptor (V\n                    <jats:sub>2<\/jats:sub>\n                    ) antagonist, is in development for the treatment of congestive heart failure and hyponatremia. Tolvaptan is primarily metabolized via CYP3A4. This study was conducted to determine the extent of the pharmacokinetic interaction between tolvaptan and steady state amiodarone, an antiarrhythmic drug commonly prescribed for patients with congestive heart failure and a known inhibitor of other drugs metabolized by CYP3A4.\n                  <\/jats:p>\n                  <jats:p>Methods: This was a multicenter, open-label, 1-arm, 3-period, sequential treatment study conducted in 11 men (10) and women aged 49 to 80 years. They were primarily Caucasian (20) subjects, with a history of cardiac arrhythmias who were otherwise healthy. Subjects were to have been on oral amiodarone maintenance therapy of 200 mg\/day for at least 10 months. All subjects took 200 mg amiodarone once daily on each study day; on days 3 and 4, they were also coadministered 30 and 90 mg of tolvaptan, respectively. The plasma concentrations of amiodarone and its metabolite desethylamiodarone were determined for 24 hours postdose on days 2, 3, and 4, tolvaptan concentrations were determined for 24 hours postdose on days 3 and 4.<\/jats:p>\n                  <jats:p>Results: As determined by the ratio of the geometric means and 90% confidence intervals (0.5 to 2.0) for the maximal plasma concentration and the area under the curve during the dosing interval for both amiodarone and desethylamiodarone, tolvaptan coadministration had no effect on either amiodarone and desethylamiodarone disposition, as all the geometric mean ratios (amiodarone + tolvaptan [30 or 90 mg] vs amiodarone alone) were approximately 1.<\/jats:p>\n                  <jats:p>Conclusion: Tolvaptan coadministration does not alter steady-state amiodarone or desethylamiodarone concentrations. Tolvaptan concentrations did not appear to be different from historical controls. The most frequently reported adverse event was polyuria (15 of 21 subjects for amiodarone + 30 mg tolvaptan); an expected outcome due to the known potent aquaretic action of tolvaptan. The combination of amiodarone and tolvaptan was well tolerated.<\/jats:p>","DOI":"10.1177\/107424840501000304","type":"journal-article","created":{"date-parts":[[2006,3,31]],"date-time":"2006-03-31T17:38:30Z","timestamp":1143826710000},"page":"165-171","source":"Crossref","is-referenced-by-count":24,"title":["Tolvaptan Administration Does Not Affect Steady State Amiodarone Concentrations in Patients With Cardiac Arrhythmias"],"prefix":"10.1177","volume":"10","author":[{"given":"Susan Elizabeth","family":"Shoaf","sequence":"first","affiliation":[{"name":"Otsuka Maryland Research Institute, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo V\u00edctor","family":"Elizari","sequence":"additional","affiliation":[{"name":"Hospital Ramos Mej\u00eda, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Otsuka Maryland Research Institute, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumara","family":"Sekar","sequence":"additional","affiliation":[{"name":"Otsuka Maryland Research Institute, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana Rosa","family":"Grinfeld","sequence":"additional","affiliation":[{"name":"Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. Alejandro","family":"Barbagelata","sequence":"additional","affiliation":[{"name":"Hospital Italiano de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Lerman","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven Lee","family":"Bramer","sequence":"additional","affiliation":[{"name":"Otsuka Maryland Research Institute, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Trong\u00e9","sequence":"additional","affiliation":[{"name":"Institutos M\u00e9dicos Ant\u00e1rtida, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesare","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Otsuka Maryland Research Institute, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2005,7,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(96)00452-3"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(76)90807-9"},{"key":"atypb3","first-page":"VI-102","volume":"87","author":"Carson PE","year":"1993","journal-title":"Circulation"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.84.1.40"},{"key":"atypb5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0735-1097(98)00297-6","volume":"32","author":"Dries DL","year":"1998","journal-title":"J Am Coll Cardiol"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.1999.2107"},{"key":"atypb7","first-page":"890","volume-title":"Heart Disease: A Textbook of Cardiovascular Medicine","author":"Myerburg RJ","year":"2001","edition":"6"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.20.2447"},{"key":"atypb9","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.12.3198"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(89)90030-2"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91895-3"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(87)90711-3"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)09145-3"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.17.2268"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)05281-1"},{"key":"atypb16","volume-title":"Wyeth-Ayerst Pharmaceuticals. 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