{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T16:38:42Z","timestamp":1758127122303},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"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":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The JTpeak interval has been proposed as a new biomarker to demonstrate mixed ion channel effects, potentially leading to reduced late\u2010stage electrocardiogram (ECG) monitoring for mildly QT\u2010prolonging drugs. ECG waveforms from the IQ\u2010CSRC study were used. Twenty healthy subjects were enrolled with 6 subjects on placebo and 9 subjects on each of 5 mildly QT\u2010prolonging drugs \u2014 moxifloxacin, dofetilide, ondansetron, dolasetron, and quinine \u2014 and 1 negative drug, levocetirizine. A vector magnitude lead was derived from 12\u2010lead ECGs, and measurements were made on a median beat from three 10\u2010second replicates. Data were analyzed using a linear concentration\u2010response model with QTcF and heart rate corrected JTpeak (JTpeak_c) as dependent variables. For moxifloxacin, dofetilide, and ondansetron, all pure hERG blockers, slopes of the concentration (C)\u2010QTcF and C\u2010JTpeak_c relationships were positive and statistically significant. With the prespecified linear model, the predicted effects on \u0394\u0394QTcF and \u0394\u0394JTpeak_c were 11.4 and 9.4\u00a0milliseconds for moxifloxacin at the geometric mean C<jats:sub>max<\/jats:sub> on day 1, 9.0 and 11.7\u00a0milliseconds for dofetilide and 11.5, and 7.9\u00a0milliseconds for ondansetron, respectively. In contrast, dolasetron and quinine, both with additional ion channel effects, prolonged QTcF with a positive C\u2010\u0394QTcF slope and predicted \u0394\u0394QTcF effect on day 1 of 6.2 and 11.4\u00a0milliseconds, whereas the C\u2010\u0394JTpeak_c slope and the predicted \u0394\u0394JTpeak on day 1 were negative (\u22120.3 and \u22127.5\u00a0milliseconds per ng\/mL). Pure hERG\u2010blocking drugs prolonged both the QTc and the JTpeak_c intervals, whereas drugs with mixed ion channel effects, including peak sodium inhibition, prolonged QTcF but not the JTpeak_c interval.<\/jats:p>","DOI":"10.1002\/jcph.1502","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T07:58:51Z","timestamp":1564991931000},"page":"125-139","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of the Effect of 5 QT\u2010Positive Drugs on the JTpeak Interval \u2014 An Analysis of ECGs From the IQ\u2010CSRC Study"],"prefix":"10.1002","volume":"60","author":[{"given":"Borje","family":"Darpo","sequence":"first","affiliation":[{"name":"ERT  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Benson","sequence":"additional","affiliation":[{"name":"Eli Lilly &amp; Company  Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy","family":"Brown","sequence":"additional","affiliation":[{"name":"ERT  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Dota","sequence":"additional","affiliation":[{"name":"AstraZeneca  Goteborg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Ferber","sequence":"additional","affiliation":[{"name":"Statistik Georg Ferber GmbH  Riehen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Ferry","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Eisai  Woodcliff Lake New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkat","family":"Jarugula","sequence":"additional","affiliation":[{"name":"Novartis  East Hannover New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Keirns","sequence":"additional","affiliation":[{"name":"Retired; at the time of the IQ\u2010CSRC study at Astellas  Northbrook Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Ortemann\u2010Renon","sequence":"additional","affiliation":[{"name":"Sanofi  Bridgewater New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuan","family":"Pham","sequence":"additional","affiliation":[{"name":"ERT  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Riley","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  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