QT and QTc Interval With Standard and Supratherapeutic Doses of Darifenacin, a Muscarinic M 3 Selective Receptor Antagonist for the Treatment of Overactive Bladder

• Published in: Journal of clinical pharmacology Vol. 45; no. 9; pp. 1038 - 1047
• Main Authors: Serra, Denise B., Affrime, Melton B., Bedigian, Martin P., Greig, Gerard, Milosavljev, Slavica, Skerjanec, Andrej, Wang, Yibin
• Format: Journal Article
• Language: English
• Published: 01-09-2005
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270005279010

Prolongation of QT interval on an electrocardiogram is a valuable predictor of a drug's ability to cause potentially fatal ventricular tachyarrhythmia (torsades de pointes). Darifenacin is a muscarinic M
3
selective receptor antagonist developed for the treatment of overactive bladder, a debilitating condition that is particularly prevalent in the older population. This 7‐day, randomized, parallel‐group study (n = 188) measured QT/QTc interval in healthy volunteers receiving once‐daily darifenacin at steady‐state therapeutic (15 mg) and supratherapeutic (75 mg) doses, alongside controls receiving placebo or moxifloxacin (positive control, 400 mg) once daily. There was no significant increase in QTcF interval with darifenacin treatment compared with placebo. Mean changes from baseline at pharmacokinetic T
max
versus placebo were −0.4 and −2.2 milliseconds in the darifenacin 15 mg and 75 mg groups, respectively, compared with +11.6 milliseconds in the moxifloxacin group (P <.01). This study demonstrates that darifenacin does not prolong QT/QTc interval.