{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T16:57:02Z","timestamp":1743267422937},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,8,31]],"date-time":"2006-08-31T00:00:00Z","timestamp":1156982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:sec><jats:title>Summary<\/jats:title><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>RWJ\u2010351647 is a selective V<jats:sub>2<\/jats:sub> receptor antagonist that inhibits vasopressin\u2010induced water reabsorption in the kidney.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the safety and tolerability of RWJ\u2010351647 compared with placebo after single oral dose administration to patients with cirrhosis and ascites, on a stable treatment with furosemide and spironolactone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Single oral doses of 1, 2 and 5\u2003mg of RWJ\u2010351647 were administered to 24 patients with ascites on stable concomitant diuretic treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RWJ\u2010351647 had a <jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub> of 1 to 1.1\u2003h and mean half\u2010life of 10.4\u201317.4\u2003h. There was no affect on the pharmacokinetics of concomitant diuretics. Increases in cumulative urine volume and free water excretion, and a decrease in urine osmolality were noted in a dose\u2010dependent manner reaching the statistical significance at the 5\u2010mg dose. Four patients exhibited a decrease of &gt;2\u2003kg in weight in the 24\u2003h after dosing. RWJ\u2010351647 was well tolerated, with no evidence of a dose\u2010related increase in adverse events when compared with placebo. No changes in either serum chemistry or plasma AVP (arginine vasopressin) and renin levels were observed despite the observed aquaresis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RWJ\u2010351647 is an effective aquaretic causing dose\u2010dependent increases in urine output and free water clearance, when co\u2010administered with conventional diuretics in patients with cirrhosis and ascites.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2036.2006.03088.x","type":"journal-article","created":{"date-parts":[[2006,8,31]],"date-time":"2006-08-31T09:39:32Z","timestamp":1157017172000},"page":"973-982","source":"Crossref","is-referenced-by-count":17,"title":["Oral V<sub>2<\/sub> receptor antagonist (RWJ\u2010351647) in patients with cirrhosis and ascites: a randomized, double\u2010blind, placebo\u2010controlled, single ascending dose study"],"prefix":"10.1111","volume":"24","author":[{"given":"P. J.","family":"THULUVATH","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"MAHESHWARI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"WONG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. W.","family":"YOO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. W.","family":"SCHRIER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"PARIKH","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"STEARE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"KORULA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,8,31]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280337"},{"key":"e_1_2_6_3_2","volume-title":"Aquaretic Efficacy of RWJ\u2010351647 after Repeated Administration in the Rat (DD02023)","author":"Gunnet JW"},{"key":"e_1_2_6_4_2","volume-title":"Aquaretic Efficacy of RWJ\u2010351647 in Cynomolgus Monkeys (DD02024)","author":"Gunnet JW"},{"key":"e_1_2_6_5_2","volume-title":"A Randomized, Double\u2010Blind, Placebo\u2010Controlled, 14\u2010Day Multiple Dose Study of the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of Oral RWJ\u2010351647 in Healthy Male Volunteers (Protocol 351647\u2010CDE\u2010102)","author":"Frame V"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.36375"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80174-7"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(98)90107-2"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb09058.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116881"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00116-8"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc4501.099313"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50021"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50143"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000070422.41439.04"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.16.1963"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2036.2006.03088.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2036.2006.03088.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T06:13:28Z","timestamp":1697177608000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2036.2006.03088.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8,31]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1111\/j.1365-2036.2006.03088.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2036.2006.03088.x","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,8,31]]}}}