Premium
Thorough QT Study with Recommended and Supratherapeutic Doses of Tolterodine
Author(s) -
Malhotra B K,
Glue P,
Sweeney K,
Anziano R,
Mancuso J,
Wicker P
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100089
Subject(s) - moxifloxacin , tolterodine , qt interval , medicine , placebo , crossover study , pharmacokinetics , anesthesia , pharmacology , antibiotics , chemistry , biochemistry , alternative medicine , pathology , overactive bladder
The objective of our study was to determine the QTc effects of tolterodine. A crossover‐design thorough QT study of recommended (2 mg twice daily) and supratherapeutic (4 mg twice daily) doses of tolterodine, moxifloxacin (400 mg once daily), and placebo was performed. Electrocardiograms (ECGs) and pharmacokinetic samples were obtained on days 1–4; time‐matched baseline ECGs were taken on day 0. Mean placebo‐subtracted change from baseline Fridericia‐corrected QT (QTcF) during peak drug exposure on day 4 was the primary end point. Mean QTcF prolongation of moxifloxacin was 8.9 ms (machine‐read) and 19.3 ms (manual‐read). At recommended and supratherapeutic tolterodine doses, mean QTcF prolongation was 1.2 and 5.6 ms (machine‐read), respectively, and 5.0 and 11.8 ms (manual‐read), respectively. The QTc effect of tolterodine was lower than moxifloxacin. No subject receiving tolterodine exceeded the clinically relevant thresholds of 500 ms absolute QTc or 60 ms change from baseline. In conclusion, tolterodine does not have a clinically significant effect on QT interval. Clinical Pharmacology & Therapeutics (2007) 81 , 377–385. doi: 10.1038/sj.clpt.6100089