Abstract
This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400mg moxifloxacin were compared with those from 21 subjects on 160 and 320mg D,L-sotalol. T-wave morphology changes, as assessed by ΔMCS, are larger after 320mg D,L-sotalol than after 160mg D,L-sotalol; and the changes associated with 160mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of ΔQTc and ΔMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (ΔMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.
| Original language | English |
|---|---|
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 88 |
| Issue number | 1 |
| Pages (from-to) | 88-94 |
| Number of pages | 7 |
| ISSN | 0009-9236 |
| DOIs | |
| Publication status | Published - 24 Jul 2010 |
Keywords
- Adolescent
- Adult
- Algorithms
- Anti-Arrhythmia Agents
- Anti-Bacterial Agents
- Aza Compounds
- Cardiovascular Agents
- Data Interpretation, Statistical
- Electrocardiography
- Female
- Heart
- Humans
- Male
- Middle Aged
- Pharmaceutical Preparations
- Quinolines
- Risk Assessment
- Sotalol
- Torsades de Pointes
- Young Adult