Malik M, Andreas J-O, Hnatkova K, Hoeckendorff J, Cawello W, Middle M, Horstmann R, Braun M
St. Paul's Cardiac Electrophysiology, London, England.
Clin Pharmacol Ther. 2008 Nov;84(5):595-603. doi: 10.1038/clpt.2008.143. Epub 2008 Jul 23.
The potential effects of the dopamine agonist rotigotine on cardiac repolarization were studied in patients with Parkinson's disease, which affects electrocardiogram (ECG) quality. The parallel-group trial was double-blind and placebo- and positive (moxifloxacin 400 mg)-controlled. After two 24-h baseline ECGs, patients were randomized to rotigotine (n = 66) or placebo (n = 64). Twenty four-hour ECGs were recorded on days 14/15, 21/22, 28/29, 35/36, and 42/43 of a regimen involving weekly dose escalations of 4 mg/24 h (4 mg/24 h-24 mg/24 h). In 10-s ECGs (n = 357,948) selected from 24-h records, QT measurements were manually verified and individually rate-corrected (QTc). Assay sensitivity showed maximum mean 13.5 ms QTc prolongation after moxifloxacin with 95% confidence interval (CI) 11.8-15.2 ms. Rotigotine vs. placebo differences in time-matched changes from baseline (54 data points/24 h) showed mean effects close to zero with upper one-sided 95% CI <5 ms. Accurate, thorough QTc studies are possible even in patients with diseases that profoundly affect ECG quality. Rotigotine in supra- and therapeutic doses was shown not to affect cardiac repolarization.
在影响心电图（ECG）质量的帕金森病患者中，研究了多巴胺激动剂罗替戈汀对心脏复极化的潜在影响。该平行组试验为双盲试验，采用安慰剂和阳性对照（莫西沙星400mg）。在进行两次24小时基线心电图检查后，患者被随机分为罗替戈汀组（n = 66）或安慰剂组（n = 64）。在一个每周剂量递增4mg/24小时（4mg/24小时 - 24mg/24小时）的治疗方案的第14/15天、21/22天、28/29天、35/36天和42/43天记录24小时心电图。在从24小时记录中选取的10秒心电图（n = 357,948）中，QT测量值经过人工验证并进行个体心率校正（QTc）。分析灵敏度显示，服用莫西沙星后平均最大QTc延长13.5毫秒，95%置信区间（CI）为11.8 - 15.2毫秒。罗替戈汀与安慰剂相比，与基线相比时间匹配变化的差异（每24小时54个数据点）显示平均效应接近零，单侧95%CI <5毫秒。即使在对心电图质量有严重影响的疾病患者中，也可以进行准确、全面的QTc研究。结果表明，治疗剂量及以上的罗替戈汀不会影响心脏复极化。
