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Thorough QT study with recommended and supratherapeutic doses of tolterodine.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2007 Mar; Vol. 81 (3), pp. 377-85. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Adult
Anti-Bacterial Agents pharmacokinetics
Area Under Curve
Aza Compounds pharmacokinetics
Benzhydryl Compounds adverse effects
Cresols adverse effects
Cross-Over Studies
Cytochrome P-450 CYP2D6 genetics
Cytochrome P-450 CYP2D6 metabolism
Double-Blind Method
Female
Fluoroquinolones
Genotype
Heart Rate drug effects
Humans
Male
Middle Aged
Models, Statistical
Moxifloxacin
Muscarinic Antagonists adverse effects
Phenylpropanolamine adverse effects
Quinolines pharmacokinetics
Tolterodine Tartrate
Benzhydryl Compounds administration & dosage
Cresols administration & dosage
Electrocardiography drug effects
Muscarinic Antagonists administration & dosage
Phenylpropanolamine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9236
- Volume :
- 81
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 17339867
- Full Text :
- https://doi.org/10.1038/sj.clpt.6100089