Somberg John C, Preston Richard A, Ranade Vasant, Molnar Janos
Division of Clinical Pharmacology, Rush University, Chicago, Ill., USA.
Cardiology. 2010;116(3):219-25. doi: 10.1159/000316050. Epub 2010 Aug 7.
The aim of this study was to evaluate the correlation between QT interval (QT) and serum sotalol concentration following a single low dose of oral and intravenous sotalol.
Fifteen healthy volunteers received 75 mg intravenous sotalol over 2.5 h and 80 mg oral sotalol in a random order. Serum sotalol concentrations and 12-lead electrocardiograms were obtained simultaneously at baseline and 7 times following dosings. Rate-corrected QT (QTc) was calculated by the Bazett, Fridericia and Framingham formulas. Linear regression analysis was performed between sotalol concentrations and QT measurements.
Significant QT prolongation was seen at very low sotalol doses and serum concentrations. QTc intervals calculated by the Framingham and Fridericia formulas showed the strongest and virtually identical correlations with serum sotalol concentration (r >or= 0.97, p < 0.001) following oral and intravenous administrations. The equation QTc = 0.0342 (sotalol concentration) + 398 closely predicted actual QTc at any sotalol concentration.
A strong correlation was observed between serum sotalol concentration and QTc prolongation across the entire concentration range. Low-dose sotalol caused significant QT prolongation. At similar concentrations, intravenous and oral sotalol caused similar QT and QTc effects. Knowing the QT effect can be used to guide further dose increase.
本研究旨在评估单次低剂量口服和静脉注射索他洛尔后QT间期（QT）与血清索他洛尔浓度之间的相关性。
15名健康志愿者随机接受2.5小时内静脉注射75毫克索他洛尔和口服80毫克索他洛尔。在基线及给药后7个时间点同时获取血清索他洛尔浓度和12导联心电图。采用Bazett、Fridericia和Framingham公式计算心率校正QT（QTc）。对索他洛尔浓度与QT测量值进行线性回归分析。
在非常低的索他洛尔剂量和血清浓度下即可观察到明显的QT延长。口服和静脉给药后，采用Framingham和Fridericia公式计算的QTc间期与血清索他洛尔浓度显示出最强且几乎相同的相关性（r≥0.97，p<0.001）。方程QTc = 0.0342（索他洛尔浓度）+ 398能紧密预测任何索他洛尔浓度下的实际QTc。
在整个浓度范围内，血清索他洛尔浓度与QTc延长之间观察到强相关性。低剂量索他洛尔可导致明显的QT延长。在相似浓度下，静脉注射和口服索他洛尔产生相似的QT和QTc效应。了解QT效应可用于指导进一步增加剂量。
