QT prolongation and serum sotalol concentration are highly correlated following intravenous and oral sotalol.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Somberg
John C
JC
Division of Clinical Pharmacology, Rush University, Chicago, Ill., USA. jsomberg@rush.edu
Preston
Richard A
RA
Ranade
Vasant
V
Molnar
Janos
J
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000187:drug effects*; D005431:Florida; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D008133:Long QT Syndrome / Q000139:chemically induced*; D008875:Middle Aged; D013015:Sotalol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D055815:Young Adult
D000889:Anti-Arrhythmia Agents; D013015:Sotalol