{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:26:50Z","timestamp":1757701610969},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T00:00:00Z","timestamp":1507680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Chelsea Therapeutics"},{"name":"Lundbeck, Deerfield Illinois, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A double\u2010blind, 4\u2010period crossover study (NCT01327066) was conducted to assess the effect of the novel norepinephrine prodrug droxidopa on the QT interval in in healthy subjects. Subjects were randomized to receive a single dose of droxidopa 600 mg (maximal dose) and 2000 mg (supratherapeutic dose) compared with the positive control, moxifloxacin 400 mg, and placebo, each separated by a 3\u2010day washout period. Patients were monitored by continuous Holter monitoring, and electrocardiograms (ECGs) were extracted 0.5\u201323 hours after dosing. Blood samples for pharmacokinetic analysis were collected before dosing and after ECG data collection. The primary end point was the time\u2010matched placebo\u2010adjusted change from baseline in the individually corrected QT (QTcI). The time\u2010averaged QTcI mean placebo\u2010corrected changes from baseline for droxidopa 600 and 2000 mg were 0.1 milliseconds (90%CI, \u20100.9 to 1.0 milliseconds) and 0.3 milliseconds (90%CI, \u20100.6 to 1.3 milliseconds), respectively, and 9 milliseconds (90%CI, 8.4\u201310.3 milliseconds) for moxifloxacin. This study found no effect of either dose of droxidopa on cardiac repolarization using QTcI. Analysis of the pharmacokinetic\/pharmacodynamic relationship and cardiac repolarization showed no association with droxidopa exposure. There were no clinically relevant effects of droxidopa on heart rate, atrioventricular conduction, or cardiac depolarization identified. No morphologic ECG changes were observed.<\/jats:p>","DOI":"10.1002\/cpdd.393","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T00:28:39Z","timestamp":1507768119000},"page":"332-340","source":"Crossref","is-referenced-by-count":7,"title":["Impact of the Norepinephrine Prodrug Droxidopa on the QTc Interval in Healthy Individuals"],"prefix":"10.1002","volume":"7","author":[{"given":"William B.","family":"White","sequence":"first","affiliation":[{"name":"Division of Hypertension and Clinical Pharmacology Calhoun Cardiology Center University of Connecticut School of Medicine  Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. Arthur","family":"Hewitt","sequence":"additional","affiliation":[{"name":"Lundbeck  Deerfield IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali A.","family":"Mehdirad","sequence":"additional","affiliation":[{"name":"Section of Cardiac Electrophysiology The Center for Comprehensive Cardiovascular Care St. Louis University Hospital and School of Medicine  St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-011-0119-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.2015.1057504"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8375-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04035"},{"issue":"1","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3233\/JPD-130259","article-title":"Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A).","volume":"4","author":"Hauser RA","year":"2014","journal-title":"J Parkinsons Dis"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26086"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000615"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010363476"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-014-0542-z"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-004-0221-z"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000083721.49847.D7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00605999"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03660.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.89.11.1363"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra032426"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003723"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2898"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1704898"},{"issue":"2","key":"e_1_2_8_20_1","first-page":"101","article-title":"Mortality and prognosis in patients with neurogenic orthostatic hypotension","volume":"27","author":"Maule S","year":"2012","journal-title":"Funct Neurol"},{"key":"e_1_2_8_21_1","unstructured":"US Department of Health and Human Services.Guidance for Industry: E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs October2005.http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm073153.pdf. 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