{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:45:31Z","timestamp":1780573531719,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This single\u2010center, randomized, 3\u2010way crossover thorough QT study evaluated the effect of steady\u2010state supratherapeutic venlafaxine (Effexor) on cardiac repolarization. Fifty\u2010four healthy adults received double\u2010blinded extended\u2010release venlafaxine 450 mg\/d and placebo and open\u2010label positive\u2010control moxifloxacin 400 mg. The postdose QT intervals corrected for heart rate using the Fridericia formula (QTcF) were assessed on day 14 with an analysis of covariance using a mixed\u2010effects model. At each time, the upper bound of the 2\u2010sided 90%CI for time\u2010matched least\u2010squares (LS) mean difference between venlafaxine and placebo did not exceed the predefined cutoff of 10 milliseconds; the highest 90%CI upper bound was 5.8 milliseconds 24\u00a0hours postdose, demonstrating the lack of effect of venlafaxine on the QTc interval (primary objective). Assay sensitivity was established because the lower bound of the 2\u2010sided 90%CI for LS mean difference in QTcF between moxifloxacin and placebo was 7.413 milliseconds on day 14 (postdose 3\u00a0hours). The exposure\u2010response analysis demonstrated no evidence of increase in QTcF with increase in venlafaxine and desvenlafaxine concentrations. Also, supratherapeutic venlafaxine was found to be safe and well tolerated. Overall, the results demonstrated the lack of significant prolongation of the QTc interval with supratherapeutic venlafaxine 450 mg\/d.<\/jats:p>","DOI":"10.1002\/cpdd.989","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T20:55:48Z","timestamp":1625864148000},"page":"100-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lack of an Effect of Supratherapeutic Dose of Venlafaxine on Cardiac Repolarization in Healthy Subjects"],"prefix":"10.1002","volume":"11","author":[{"given":"Richat","family":"Abbas","sequence":"first","affiliation":[{"name":"Medical Product Evaluation Upjohn, Pfizer Inc.  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Riley","sequence":"additional","affiliation":[{"name":"Global Product Development Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Nepal","sequence":"additional","affiliation":[{"name":"SKN Statistical Consulting Services LLC  Schwenksville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Bachinsky","sequence":"additional","affiliation":[{"name":"Global Product Development Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Global Product Development Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip B.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Global Product Development Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Damle","sequence":"additional","affiliation":[{"name":"Global Research and Development Pfizer Inc.  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Drugs@FDA: FDA\u2010Approved Drugs.https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=overview.process&varApplNo=020699. Accessed May 3 2021."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199549020-00010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200115080-00007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1520-765X(01)90010-0"},{"issue":"1","key":"e_1_2_10_6_1","first-page":"53","article-title":"Drug\u2010induced QT prolongation and sudden death","volume":"107","author":"Del Rosario ME","year":"2010","journal-title":"Mol Med"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.9740\/mhc.2016.07.165"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0000000000000124"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.749"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.51"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318030aff7"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2005.03.065"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajp.2015.06.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.02849.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03382.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03160945"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650701358755"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psym.2017.10.009"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1520-6394(2000)12:1 <30::AID-DA4>3.0.CO;2-G"},{"key":"e_1_2_10_20_1","volume-title":"NR571 \u2010 Double\u2010Blind, Placebo\u2010 and Moxifloxacin\u2010Controlled Crossover Study of the Effects of Desvenlafaxine Succinate on QT Interval in Healthy Adult Female Subjects","author":"Paul J","year":"2006"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00487.x"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.989","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.989","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.989","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T13:39:24Z","timestamp":1693229964000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/cpdd.989"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.989","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,9]]},"assertion":[{"value":"2021-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}